CD44 isoforms have been implicated in tumor progression and embryogenesis. Primary renal cell tumors (n = 100) of various histopathological differentiation and grading stages were analyzed for expression of CD44 isoforms in comparison with nonmalignant adult and fetal renal tissues. Evaluations were performed by immunohistochemistry using ...

CD44 is observed in ureteric bud structures and is implicated in branching morphogenesis during early mouse renal development. Healthy adult kidney demonstrates minimal CD44, but CD44 is up-regulated in renal diseases. CD44 may mediate binding of ...

Dendritic cells (DCs) express CD44, a cell surface receptor for the extracellular matrix ligand hyaluronate, involved in cell-cell interactions and cell migration. Besides the "standard" form of CD44, a variety of splice variants contain an additional extracellular region encoded by 10 "variable" exons termed v1 to v10. The standard form of CD44 as well as ...

High expression of EpCAM and the tetraspanin CO-029 has been associated with colorectal cancer progression. However, opposing results have been reported on CD44 variant isoform v6 (CD44v6) expression. We recently noted in rat gastrointestinal tumors that EpCAM, claudin-7, CO-029, and CD44v6 were frequently coexpressed and could form a complex. This finding ...

Podoplanin is a transmembrane glycoprotein up-regulated in different human tumors, especially those derived from squamous stratified epithelia (SCCs). Its expression in tumor cells is linked to increased cell migration and invasiveness; however, the mechanisms underlying this process remain poorly understood. Here we report that CD44, the major hyaluronan (HA) receptor, is a ...

Epithelial-mesenchymal transition (EMT) is a tightly regulated process that is critical for embryogenesis but is abnormally activated during cancer metastasis and recurrence. Here we show that a switch in CD44 alternative splicing is required for EMT. Using both in vitro and in vivo systems, we have demonstrated a shift in CD44 expression from variant isoforms ...

Epithelial-mesenchymal transition (EMT) is a tightly regulated process that is critical for embryogenesis but is abnormally activated during cancer metastasis and recurrence. Here we show that a switch in CD44 alternative splicing is required for EMT. Using both in vitro and in vivo systems, we have demonstrated a shift in CD44 expression from variant isoforms ...

Tumor-initiating cells (T-ICs) discovered in various tumors have been widely reported. However, T-IC populations in salivary gland tumors have yet to be elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1) transgenic mouse model of a salivary gland tumor, we identified CD44^high ...

CD44 is an integral hyaluronan receptor that can promote or inhibit motogenic signaling in tumor cells. Rhamm is a non-integral cell surface hyaluronan receptor (CD168) and intracellular protein that promotes cell motility in culture and its expression is strongly upregulated in diseases like arthritis and aggressive cancers. Here we ...

CD44 is a widely-expressed adhesion receptor that is associated with diverse biological processes involving migrating cells, including inflammation, angiogenesis, bone metabolism and wound healing. In the immune system, CD44 is upregulated after activation of naive T lymphocytes during their ...

Hepatocyte growth factor/scatter factor (HGF/SF) can induce proliferation and motility and promote invasion of tumor cells. Since HGF/SF receptor, c-Met, is expressed by tumor cells, and since stimulation of CD44, a transmembrane glycoprotein known to bind hyaluronic acid (HA) in its extracellular domain, is involved in activation of c-Met, we have studied the effects of CD44 stimulation by ...

The cell surface hyaluronate receptor CD44 has previously been shown to have immunomodulatory activity and to be upregulated in inflammatory synovitis. Since these findings were reported, the genomic structure of CD44 has been delineated, and multiple splice variants have been described. Therefore, we determined which ...

CD44 is a cell surface receptor for the extracellular matrix glycosaminoglycan hyaluronan and is involved in processes ranging from leukocyte recruitment to wound healing. In the immune system, the binding of hyaluronan to CD44 is tightly regulated, and exposure of human peripheral blood monocytes to inflammatory stimuli increases ...

Cancer stem cells (CSCs)/tumor-initiating cells have been defined as a subset of tumor cells responsible for initiating and sustaining tumor development. Emerging evidence strongly supports the existence of CSCs in various solid tumors, but they have not yet been identified in human gallbladder carcinomas (GBC). In this study, we identified CSCs in primary GBC and in the cell line GBC-SD using the ...

BackgroundCD44, a hyaluronan (HA) receptor, is a multistructural and multifunctional cell surface molecule involved in cell proliferation, cell differentiation, cell migration, angiogenesis, presentation of cytokines, chemokines and growth factors to the corresponding receptors, and docking of proteases at the cell membrane, as well as in signaling for ...

Streptococcus pneumoniae is the most prevalent pathogen causing community-acquired pneumonia. CD44 is a transmembrane adhesion molecule, expressed by a wide variety of cell types, that has several functions in innate and adaptive immune responses. In this study, we tested the hypothesis that CD44 is involved in the host response during pneumococcal ...

Allergic asthma is a chronic inflammatory disease characterized by the infiltration of inflammatory cells, the elevated production of cytokines and enhanced airway hyperreactivity (AHR). CD44 is a widely expressed cell adhesion molecule that is involved in lymphocyte adhesion to inflamed endothelium. Previous studies showed that pulmonary eosinophils and ...

Tissue inhibitor of metalloproteinase-1 (TIMP1) is a survival factor of germinal center (GC) B cells, and its over-expression is correlated with aggressive B cell lymphomas and classical Hodgkin lymphomas. We previously demonstrated that TIMP1 down-regulates B-cell receptor and BCL6, and activates interleukins-6,-10 (ILs)/signal transducer and activator of transcription-3 (STAT3) signaling in GC B ...

Increased expression of CD44 variant isoforms have been shown on the inflammatory infiltrates in human and mouse colitis and blockade or deletion of CD44 isoforms inhibit experimental colitis. The objective of this study was to find out if short-term treatment of CD44 antibodies specific to CD44v7, but not to other variant isoforms, suppresses leucocyte�endothelial interaction in chronic dextran ...

The complex system involved in the synthesis, degradation, and binding of the high molecular weight glycosaminoglycan hyaluronic acid (hyaluronan or HA) provides a variety of structures that can be exploited for targeted cancer therapy. In many cancers of epithelial origin there is an up-regulation of CD44, a receptor that binds HA. In other cancers, HA in the tumor matrix is ...

In the present work it was investigated if a spontaneous alteration of the native melanotic transplantable melanoma form into amelanotic form, connected with the tumor progression, is accompanied by changes of CD44 surface glycoprotein expression. We also tried to find out if there exists any correlation between changes in CD44 expression and IL-6, TNF-alpha, and IL-10 ...

CD44 on macrophages is recognized as a phagocytic receptor involved in the phagocytosis of apoptotic cells. Recently, we detected CD44 on macrophages in atretic follicles during atresia. In this study, we evaluated the distribution of the principal CD44 ligand hyaluronan ...

Purpose:T cells are essential for the development of autoimmune uveitis. Although the co-stimulatory molecule OX40 promotes T cell function and expansion, it is unclear if OX40 is implicated in ocular inflammation. The purpose of this study was to examine the role of OX40 in uveitis.Methods:Experimental autoimmune uveitis (EAU) was induced in B10.RIII mice by subcutaneous injection of ...

Upon antigen contact, epidermal Langerhans cells (LC) and dendritic cells (DC) leave peripheral organs and home to lymph nodes via the afferent lymphatic vessels and then assemble in the paracortical T cell zone and present antigen to T lymphocytes. Since splice variants of CD44 promote metastasis of certain tumors to lymph nodes, we explored the expression of CD44 proteins on migrating LC ...

We previously found that bikunin (bik), a Kunitz-type protease inhibitor, suppresses phorbol ester (PMA)-stimulated expression of urokinase-type plasminogen activator (uPA). In the present study, we tried to answer this mechanism using human chondrosarcoma HCS-2/8 cells. Our results showed the following novel findings: (a) the standard form of CD44 (CD44s; ...

... Page 2. AD Award Number: DAMD17-97-1-7045 TITLE: Vascular CD44 Expression and Breast Cancer Angiogenesis and Metastasis ...

... Title : Osteopontin CD44 Interaction: A Novel Mechanism for the Selective Homing of Breast Tumor Cells into Bone. Descriptive Note : Final rept. ...

... Mitogen-activated protein kinase (MAPK) pathways and paracrine calcitonin may dysregulate CD44. CD44 total and CD44v7 ...

Mis-expression of microRNAs (miRNA) is widespread in human cancers, including in pancreatic cancer. Aberrations of miRNA include overexpression of oncogenic miRs (Onco-miRs) or downregulation of so-called tumor suppressor TSG-miRs. Restitution of TSG-miRs in cancer cells through systemic delivery is a promising avenue for pancreatic cancer therapy. We have synthesized a lipid-based nanoparticle ...

BackgroundTranslational control mediated by non-coding microRNAs (miRNAs) plays a key role in the mechanism of cellular resistance to anti-cancer drug treatment. Dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS, TS) are two of the most important targets for antifolate- and fluoropyrimidine-based chemotherapies in the past 50 years. In this study, we investigated the roles of miR-215 ...

Hyaluronan is an oligosaccharide found in the pericellular matrix of numerous cell types and hyaluronan induced signaling is known to facilitate fibrosis and cancer progression in some tissues. Hyaluronan is also commonly instilled into the eye during cataract surgery to protect the corneal endothelium from damage. Despite this, little is known about the distribution of hyaluronan or its receptors ...

The regulation of CD44v6, a variant of the CD44 family of glycosylated adhesions molecules, through HGF (hepatocyte growth factor) has implications for motility in primary human melanocytes. We demonstrate that exposure of primary human melanocytes to HGF results in an increase of CD44v6 expression. Immunostaining of melanocytic lesions revealed low, cytoplasmic positivity of CD44v6 in some nevi, ...

BACKGROUND--Studies have suggested that expression of the adhesion molecule CD44 may be of prognostic importance in gastric cancer. In addition, there is strong evidence that Helicobacter pylori has a role in gastric cancer. AIMS--To determine the expression of CD44 and its variants (v6, v9) and HLA class II molecules on human gastric epithelial cell and ...

PurposeEvidence is lacking whether the number of breast tumor-initiating cells (BT-ICs) directly correlates with the sensitivity of breast tumors to chemotherapy. Here, we evaluated the association between proportion of BT-ICs and chemoresistance of the tumors.MethodsImmunohistochemical staining(IHC) was used to examine the expression of aldehyde dehydrogenase 1 (ALDH1) and proliferating cell ...

Multidrug resistance and disease relapse is a challenging clinical problem in the treatment of breast cancer. In this study, we investigated the hyaluronan (HA)-induced interaction between CD44 (a primary HA receptor) and protein kinase Cepsilon (PKCepsilon), which regulates a number of human breast tumor cell functions. Our results indicate that HA ...

Multidrug resistance and disease relapse is a challenging clinical problem in the treatment of breast cancer. In this study, we investigated the hyaluronan (HA)-induced interaction between CD44 (a primary HA receptor) and protein kinase C? (PKC?), which regulates a number of human breast tumor cell functions. Our results indicate that HA binding to CD44 ...

It has been established that fragmented hyaluronic acid (HA), but not native high molecular weight HA, can induce angiogenesis, cell proliferation and migration. We have studied the outside-in signal transduction pathways responsible for fragmented HA-mediated cancer cell invasion. In our study, we have studied the effects of CD44 stimulation by ligation with HA upon the expression of matrix ...

In this study we have investigated hyaluronan (HA)-mediated CD44 (an HA receptor) interactions with p300 (a histone acetyltransferase) and SIRT1 (a histone deacetylase) in human breast tumor cells (MCF-7 cells). Specifically, our results indicate that HA binding to CD44 up-regulates p300 expression and its acetyltransferase activity ...

Proteoglycan expression patterns in the central nervous system guide neuronal pathfinding during development, but also disrupt regeneration after injuries. To deepen our understanding of the molecular level effects of proteoglycan spatial arrangements on neuronal pathfinding, we designed micropatterning stamps for the precise placement of near single molecule chondroitin sulfate proteoglycan ...

Oligosaccharides of hyaluronan (o-HA) can induce angiogenesis and the growth and tube formation of vascular endothelial cells (ECs) in particular. As the major o-HA receptor, CD44 has been implicated in EC function, but its role in mediating o-HA-induced EC proliferation and tube formation remains unclear. In this study, we investigated the role of CD44 in ...

The activating transcription factor 3 (ATF3) gene is induced by a variety of signals, including many of those encountered by cancer cells. We present evidence that ATF3 is induced by TGF? in the MCF10CA1a breast cancer cells and plays an integral role for TGF? to upregulate its target genes snail, slug and twist, and to enhance cell motility. Furthermore, ATF3 ...

Dysregulation of microRNAs is observed in many cancers, including breast cancer. In particular, miR-10b appears to play an important role in tumor cell invasion and breast cancer progression. In this study, we investigated hyaluronan (HA)-induced CD44 (a primary HA receptor) interaction with c-Src kinase and the transcriptional factor, Twist, in breast ...

The cell adhesion molecule CD44 is encoded by a complex gene and undergoes extensive alternative splicing. Differential regulation of CD44 splicing has been implicated in human tumorigenesis, and differences in variant isoform expression in normal versus ...

Here, we identify CD44(+)CD90(+)CD73(+)CD34(?)CD45(?) cells within the adult human arterial adventitia with properties of multipotency which were named vascular wall-resident multipotent stem cells (VW-MPSCs). VW-MPSCs exhibit typical mesenchymal stem cell characteristics including cell surface markers in immunostaining and flow cytometric analyses, and ...

DNA-damaging agents cause a multifaceted cellular stress response. Cells set in motion either repair mechanisms or programmed cell death pathways, depending on the extent of the damage and on their ability to withstand it. The RNA-binding protein (RBP) Sam68, which is up-regulated in prostate carcinoma, promotes prostate cancer cell survival to genotoxic stress. Herein, we ...

Considerable levels of testosterone and dihydrotestosterone (DHT) are found in prostate cancer (PCa) tissue after androgen deprivation therapy. Treatment of surviving cancer-initiating cells and the ability to metabolize steroids from precursors may be the keystones for the appearance of recurrent tumors. To study this hypothesis, we assessed the expression of several steroidogenic enzymes and ...

Aging is a result of damage accumulation, and understanding of the mechanisms of aging requires exploration of the cellular and molecular systems functioning to control damage. Senescence-accelerated mouse prone 10 (SAMP10) has been established as an inbred strain exhibiting accelerated aging with an earlier onset of cognitive impairment due to neurodegeneration than the senescence-resistant ...

cD44 is the major hyaluronan cell surface receptor, and functions as an adhesion molecule in many different cell types including human breast epithelial cells. The coexpression of certain CD44 variants (CD44v), such as CD44v (v10/ex14), with CD44s (standa...

Loss of CD44 standard and increased splice variant form CD44v7-10 facilitate prostate cancer (PC) invasion. Mitogen-activated protein kinase (MAPK) pathways and paracrine calcitonin may dysregulate CD44. CD44 total and CD44v7-10 RNA or protein were assess...

ADAMTS5 has been implicated in the degradation of cartilage aggrecan in human osteoarthritis. Here, we describe a novel role for the enzyme in the regulation of TGF?1 signaling in dermal fibroblasts both in vivo and in vitro. Adamts5(-/-) mice, generated by deletion of exon 2, exhibit impaired contraction and dermal collagen deposition in an excisional wound healing model. This was ...

Emk is a serine/threonine protein kinase implicated in regulating polarity, cell cycle progression, and microtubule dynamics. To delineate the role of Emk in development and adult tissues, mice lacking Emk were generated by targeted gene disruption. Emk^?/? mice displayed growth retardation and immune cell dysfunction. Although B- and T-cell development were normal, ...

We report the identification and characterization of the small subpopulation of alloantigen-specific T cells in vitro and in vivo. This subpopulation of T cells was distinguished by up-regulation of cell surface CD4 expression. These CD4high T cells were alloantigen specific in proliferation assays in vitro, and they expressed memory/activation markers, including ...

Normal human prostate (NHP) epithelial cells undergo senescence in vitro and in vivo, but the underlying molecular mechanisms remain obscure. Here we show that the senescence of primary NHP cells, which are immunophenotyped as intermediate basal-like cells expressing progenitor cell markers CD44, ?2?1, p63, hTERT, and CK5/CK18, involves loss of ...

The migration of epidermal Langerhans cells (LC) and their transport of antigen from the skin to draining lymph nodes are of considerable importance in the induction of cutaneous immune responses, including contact sensitization. While in transit to the lymph nodes, LC are subject to a number of phenotypic changes required for their movement from the skin and acquisition of the capacity for ...

Epithelial-to-mesenchymal transition (EMT) plays an important role during normal embryogenesis, and it has been implicated in cancer invasion and metastasis. Here, we report that Ladybird homeobox 1 (LBX1), a developmentally regulated homeobox gene, directs expression of the known EMT inducers ZEB1, ZEB2, Snail1, and transforming growth factor beta2 (TGFB2). In mammary epithelial cells, ...

Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC) has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, ...

BackgroundIn breast cancer cells, the metastatic cell state is strongly correlated to epithelial-to-mesenchymal transition (EMT) and the CD44⁺/CD24^- stem cell phenotype. However, the MCF-7 cell line, which has a luminal epithelial-like phenotype and lacks a CD44⁺/CD24^- subpopulation, has rare cell ...

BackgroundCancer cells are believed to arise primarily from stem cells. CD44⁺/CD24^- have been identified as markers for human breast cancer stem cells. Although, HER2 is a well known breast cancer oncogene, the mechanisms of action of this gene are not completely understood. Previously, we have derived immortal ...

CD44 isoforms have been implicated in tumor progression and metastasis formation. This study presents a thorough immunohistochemical analysis of CD44 standard and isoform expression in normal human skin appendages and epidermis applying monoclonal antibodies against CD44s, ...

CD44 and fibrin(ogen) play critical roles in the hematogenous dissemination of tumor cells, including colon carcinomas. We recently reported that CD44 is the primary fibrin, but not fibrinogen, receptor on LS174T colon carcinomas. However, the biochemical nature of this interaction and the roles of CD44 standard ...

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive and lethal disorder characterized by fibroproliferation and excessive accumulation of extracellular matrix in the lung.Methods and FindingsUsing oligonucleotide arrays, we identified osteopontin as one of the genes that significantly distinguishes IPF from normal lungs. Osteopontin was localized to alveolar epithelial cells in IPF ...

BackgroundGrowing evidence suggests that the majority of tumors are organized hierarchically, comprising a population of tumor-initiating, or cancer stem cells (CSCs) responsible for tumor development, maintenance and resistance to drugs. Previously we have shown that the CD133^high/CD44^high fraction of colon cancer cells is different from their bulk ...

Hyaluronan (HA), a glycosaminoglycan, is a major component of the pericellular matrix which envelopes mammalian cells. Binding of hyaluronan to one of its specific receptors, CD44, modulates transduction of intracellular signals which direct a variety of processes, including embryogenesis, wound healing, inflammation, and neoplasia. Since regulation of ...

4-Methylumbelliferone (4-MU) is a hyaluronic acid (HA) synthesis inhibitor with anticancer properties; the mechanism of its anticancer effects is unknown. We evaluated the effects of 4-MU on prostate cancer cells. 4-MU inhibited proliferation, motility, and invasion of DU145, PC3-ML, LNCaP, C4-2B, and/or LAPC-4 cells. At IC(50) for HA synthesis (0.4 mmol/L), 4-MU induced >3-fold apoptosis in ...

4-methylumbelliferone (4-MU) is a hyaluronic acid (HA) synthesis inhibitor with anticancer properties; the mechanism of its anticancer effects is unknown. We evaluated the effects of 4-MU on prostate cancer cells. 4-MU inhibited proliferation, motility and invasion of DU145, PC3-ML, LNCaP, C4-2B and/or LAPC-4 cells. At IC₅₀ for HA synthesis (0.4 mM), 4-MU induced > 3-fold ...

Considerable levels of testosterone and dihydrotestosterone (DHT) are found in prostate cancer (PCa) tissue after androgen deprivation therapy. Treatment of surviving cancer-initiating cells and the ability to metabolize steroids from precursors may be the keystones for the appearance of recurrent tumors. To study this hypothesis, we assessed the expression of several steroidogenic enzymes and ...

In several recent studies, CD44 expression has been associated with aggressive behavior in cancers of different types. CD44 expression is also linked to cancer stem cells, which have been shown to play a significant role in tumor progression and poor prognosis in head and neck squamous cell carcinoma (HNSCC), as ...

The CD44 family of surface receptors regulates adhesion, movement, and activation of normal and neoplastic cells. The cytokine osteopontin (Eta-1), which regulates similar cellular functions, was found to be a protein ligand of CD44. Osteopontin induces cellular chemotaxis but not homotypic aggregation, whereas the inverse is true for the interaction between ...

... The breast cancer susceptibility gene, BRCA2, has been shown to ... 9 =MCF7 breast cancer cells. ... Immunohistologic identification of cells undergoing ...

... Abstract : The breast cancer susceptibility gene, BRCA2, is thought to function during cellular proliferation, differentiation and DNA repair. ...

... Abstract : The breast cancer susceptibility gene, BRCA2, has been shown to play a role in cellular proliferation, differentiation and DNA repair. ...

BackgroundCD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether ...

ABSTRACT: BACKGROUND: CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether ...

... In this proposal, paclitaxel covalently coupled to backbones of poly(L-glutamic) acid (non-targeted) or hyaluronic acid (CD44 targeted) as prodrugs ...

... HA (Fig 1B). In collagen gels that were cast with HA, there was a decreased level of CD44 associated FAK. We looked ...

CD44, a polymorphic hyaluronate receptor, may participate in chronic inflammation. We hypothesized that CD44 variants contribute to the development of arterial diseases. CD44 levels vary in normal and diseased arterial tissues in the following order: unaffected arteries < fibrous plaques ? abdominal aortic ...

... composed of a tumor-associated CD44 alternative splicing unit (ASU) which includes alternatively spliced exons and flanking introns and exons ...

The CD44 protein family spans a large group of transmembrane glycoproteins acquired by alternative splicing and post-translational modifications. The great heterogeneity in molecular structure is reflected in its various important functions: CD44 mediates (1) interaction between cell and extracellular matrix, (2) signal submission, e.g., by acting as ...

... rise to diverse and more differentiated cell types with ... tumorigenic CD44+/CD24-( low)/Lineage-cells may, indeed, be breast tumor stem cells. ...

... to diverse and more differentiated cell types with ... tumorigenic CD44+/CD24-( low)/Lineage- cells may, indeed, be breast tumor stem cells. ...

... St cells that overexpress soluble CD44 did not accumulate ascites fluid; the transfectants grew at a reduced rate within the peritoneum, then went ...

MicroRNAs are often associated with the pathogenesis of many cancers, including head and neck squamous cell carcinoma (HNSCC). In particular, microRNA-21 (miR-21) appears to have a critical role in tumor cell survival, chemoresistance and HNSCC progression. In this study, we investigated matrix hyaluronan (HA)-induced CD44 (a primary HA receptor) ...

This study was aimed to investigate the effects of cobalt protoporphyrin (CoPP) on hyperexpression of heme oxygenase-1 (HO-1) and secretion of IL-10 in bone marrow-derived mesenchymal stem cells (BMMSC). The BMMSC were isolated from rats and cultured, then were randomly divided into 4 groups, and were induced in culture medium with CoPP of 0, 25, 50, and 75 �mol/L respectively. The expressions ...

ZAP-70 in chronic lymphocytic leukemia (CLL) has been associated with enhanced B-cell receptor (BCR) signaling, survival and migration. We investigated whether ZAP-70 can directly govern migration and the underlying mechanisms. In the ZAP-70 stably-transfected Ramos cell line, IgM stimulation but no IgD enhanced phosphorylation of ERK1/2, Akt and Syk, and delayed IgM and CD79b internalization. In ...

AIM: To investigate the immune response of peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) that were stimulated by probiotic preparations.METHODS: PBMCs were isolated, cultured, and stimulated with Bio-Three (a mixture of Bacillus mesentericus, Clostridium butyricum and Enterococcus faecalis; 10⁵, 10⁶ and 10⁷ ...

Prostate cancer remains the single most prevalent cancer in men. Standard therapies are still limited and include androgen ablation that initially causes tumor regression. However, tumor cells eventually relapse and develop into a hormone-refractory prostate cancer. One of the current challenges in this disease is to define new therapeutic targets, which have been virtually unchanged in the past ...

Inducible nitric oxide synthase (NOS2) is involved in wound healing, angiogenesis, and carcinogenesis. NOS2 upregulation and increased nitric oxide (NO) production affect the redox state of cells and can induce protein, lipid, and DNA modifications. To investigate whether NOS2 levels influence survival of breast cancer patients, we examined NOS2 expression and its association ...

Inducible nitric oxide synthase (NOS2) is involved in wound healing, angiogenesis, and carcinogenesis. NOS2 upregulation and increased nitric oxide (NO) production affect the redox state of cells and can induce protein, lipid, and DNA modifications. To investigate whether NOS2 levels influence survival of breast cancer patients, we examined NOS2 expression and its association ...

Inflammation has been recognized increasingly as a critical pathologic component of a number of heart diseases. A mouse model of autoimmune myocarditis was developed to study the role of immune mediators in the development of cardiac dysfunction. We have found previously that IFN-? deficiency promotes inflammation in murine myocarditis. It has been unclear, however, how IFN-? deficiency in ...

A small subset of cells within a malignant neoplasm, named cancer stem cells (CSCs) or tumour initiating cells, are thought to be capable of initiating the neoplasm itself, and of driving its growth and recurrence after treatment. It is unclear whether CSCs can be identified and experimentally induced within oral squamous cell carcinoma (OSCC), although this has been reported for a number of other ...

How cancer cells bind to vascular surfaces and extravasate into target organs is an underappreciated, yet essential step in metastasis. We postulate that the metastatic process involves discrete adhesive interactions between circulating cancer cells and microvascular endothelial cells. Sialyl Lewis X (sLe^X) on prostate cancer (PCa) cells is thought to promote metastasis by ...

Two actin genes cloned from Culex pipiens L. are upregulated during adult diapause. Though actins 1 and 2 were expressed throughout diapause, both genes were most highly expressed early in diapause. These changes in gene expression were accompanied by a conspicuous redistribution of polymerized acti...

� matrix adhesion molecule. CD44 pro- motes migration, presumably via binding to extracellular molecules are motile and shed soluble CD44, and yet the sur- rounding transfected cells are not mo- tile. This suggests. In vitro adhesion assays demon- strate that activated T cells adhere far more strongly to laminin ...

In the current study, we examined the potential significance of CD44 expression on lymphokine-activated killer (LAK) cells in their interaction and killing of melanoma cells. Stimulation of splenocytes with IL-2 led to a significant increase in the expression of CD44 on T cells, NK cells, and NKT cells. Treatment of melanoma-bearing CD44 WT mice with IL-2 ...

Breast cancer stem cells exist in several breast cancer cell lines based on recognized surface marker CD44+/CD24 or low or Hoechst efflux/ABCG2. The increased radiation resistance of breast cancer stem-like cells (CD44+/CD24 or low) was found in MCF-7, HC...

Stem-like cancer cells (SLCCs) are distinct cellular subpopulation in colon cancer that is essential for tumor maintenance. Previous studies indicated that SLCCs accounted for only a minor subset in a given cancer model. However, we found that SLCCs frequency varied among a panel of colon cancer cell lines, with HCT116 cells composed mainly of SLCCs, as demonstrated by colonosphere forming ...

Background/AimsCluster differentiation 44 standard isoform (CD44s) is a transmembrane glycoprotein. CD44s is a known prognostic factor in various cancers, due to its involvement in tumor cell growth, invasion and metastasis. Its prognostic role, however, is debated because it can be a positive or negative ...

Human CD44 standard isoform cDNA (hCD44s) was transfected into sis-transformed Balb/c 3T3 cells and into ras-revertant IIIA4 cells (both tumorigenic but nonmetastatic). Transfectants were injected subcutaneously into athymic nude mice to elucidate the functional role of hCD44s over-expression in progression and ...

CD44 is the major cell surface receptor for the extracellular matrix glycosaminoglycan hyaluronan and is implicated in a variety of biological events that include embryonic morphogenesis, lymphocyte recirculation, inflammation, and tumor metastasis. CD44 delivers activation signals to T lymphocytes, B lymphocytes, ...

Cell migration and phagocytosis are both important for controlling Mycobacterium tuberculosis infection and are critically dependent on the reorganization of the cytoskeleton. Since CD44 is an adhesion molecule involved in inflammatory responses and is connected to the actin cytoskeleton, we investigated the role of CD44 in both these processes. Macrophage ...

A monoclonal antibody, AF3, was previously shown to specifically inhibit poliovirus binding to HeLa cells and to detect a 100-kDa glycoprotein only in cell lines and tissues permissive for poliovirus infection. These results suggested that the 100-kDa protein may be involved in the pathogenesis of poliomyelitis and the cellular function of the poliovirus receptor site. To study further the role of ...

Invasive tumour cells, such as gliomas, frequently express EGF (epidermal growth factor) receptor at a high level and they exhibit enhanced cell migration in response to EGF. We reported previously that tumour cell migration is associated with ectodomain cleavage of CD44, the major adhesion molecule that is implicated in tumour invasion and metastasis, and that the cleavage is enhanced by ligation ...

BackgroundThe cancer stem cell theory hypothesizes that cancers are perpetuated by cancer stem cells (CSC) or tumor initiating cells (TIC) possessing self-renewal and other stem cell-like properties while differentiated non-stem/initiating cells have a finite life span. To investigate whether the hypothesis is applicable to lung cancer, identification of lung CSC and demonstration of these ...

BackgroundSeveral cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM). It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene ...

Directing differentiation of human embryonic stem cells (hESCs) into specific cell types using an easy and reproducible protocol is a prerequisite for the clinical use of hESCs in regenerative-medicine procedures. Here, we report a protocol for directing the differentiation of hESCs into mesenchymal progenitor cells. We demonstrate that inhibition of transforming growth factor beta ...

5T4 oncofetal molecules are highly expressed during development and upregulated in cancer while showing only low levels in some adult tissues. Upregulation of 5T4 expression is a marker of loss of pluripotency in the early differentiation of embryonic stem (ES) cells and forms an integrated component of an epithelial-mesenchymal transition, a process ...

BackgroundThe development of insulin resistance (IR) in mouse models of obesity and type 2 diabetes mellitus (DM) is characterized by progressive accumulation of inflammatory macrophages and subpopulations of T cells in the visceral adipose. Regulatory T cells (Tregs) may play a critical role in modulating tissue inflammation via their interactions with both adaptive and innate immune mechanisms. ...

Human amniotic epithelial cells (hAECs) are potentially one of the key players in tissue engineering due to their easy availability. The aim of the present study was to develop an optimal isolation and transportation technique, as well as to determine the immunophenotype and epithelial gene expression of hAECs. Amnion was mechanically peeled off from the chorion and digested with ...

Head and neck squamous cell carcinomas (HNSCC) are common and aggressive tumors that have not seen an improvement in survival rates in decades. These tumors are believed to evade the immune system through a variety of mechanisms and are therefore highly immune modulatory. In order to elucidate their interaction with the immune system and develop new therapies targeting immune escape, new ...

LH receptor knockout (LhrKO) male mice exhibit a bilateral cryptorchidism resulting from a developmental defect in the gubernaculum during the inguinoscrotal phase of testis descent, which is corrected by testosterone replacement therapy (TRT). In vivo and in vitro experiments were conducted to investigate the roles of the androgen receptor (AR) and RXFP2 signals in regulation of gubernacular ...

BackgroundStromal signalling increases the lateral cell adhesions of prostate epithelial cells grown in 3D culture. The aim of this study was to use microarray analysis to identify significant epithelial signalling pathways and genes in this process.MethodsMicroarray analysis was used to identify genes that were differentially expressed when epithelial cells were grown in 3D Matrigel culture with ...

It has been proven that "side population (SP)" cells that exclude Hoechst 33342 dye are enriched with cancer stem cells in several tumors. In the present study we aimed to isolate and characterize SP cells from human primary osteosarcoma. Side population cells were detected in osteosarcoma samples. In vitro, SP cells regenerated both SP and non-SP and the clonogenicity of SP cells was higher than ...

Podoplanin is a type-I transmembrane sialomucin-like protein, which is expressed in a wide range of cell types and is involved in platelet aggregation and tumor metastasis. Here, we investigated the function, regulation, and expression of podoplanin in osteosarcoma. Podoplanin expression was observed in three osteosarcoma cell lines (MG-63, HOS, and U-2 OS) with platelet aggregation-inducing ...

Despite advances in diagnosis and treatment of prostate cancer, development of metastases remains a major clinical challenge. Research efforts are dedicated to overcome this problem by understanding the molecular basis of the transition from benign cells to prostatic intraepithelial neoplasia (PIN), localized carcinoma, and metastatic cancer. Identification of proteins that inhibit dissemination ...

Cutaneous T-cell lymphomas (CTCL) represent a spectrum of several distinct non-Hodgkin's lymphomas that are characterized by an invasion of the skin by malignant, clonal lymphocytes. Our laboratory has previously demonstrated that the protein kinase C (PKC) ? inhibitor Enzastaurin increases apoptosis in malignant lymphocytes of CTCL. These results directly led to a clinical trial for Enzastaurin ...

Despite progress in the treatment of glioblastoma, more than 95% of patients suffering from this disease still die within 2 years. Recent findings support the belief that cancer stem-like cells are responsible for tumor formation and ongoing growth. Here a method combining lectin microarray and LC-MS/MS was used to discover the cell surface glycoprotein markers of a glioblastoma-derived stem-like ...

Despite progress in the treatment of glioblastoma, more than 95% of patients suffering from this disease still die within two years. Recent findings support the belief that cancer stem-like cells are responsible for tumor formation and ongoing growth. Here a method combining lectin microarray and LC-MS/MS was used to discover the cell surface glycoprotein markers of a glioblastoma-derived ...

The development of invariant NKT (iNKT) cells depends on the thymus. After positive selection by CD4(+)CD8(+)CD1d(+) cortical thymocytes, iNKT cells proceed from CD44(low)NK1.1(-) (stage 1) to CD44(high)NK1.1(-) (stage 2), and then to CD44(high)NK1.1(+) (stage 3) cells. The programming of cytokine production occurs along the three differentiation stages, ...

Hyaluronan is a glycosaminoglycan of the extracellular matrix. In tumors and during chronic inflammatory diseases, hyaluronan is degraded to smaller fragments, which are known to stimulate endothelial cell differentiation. In this study, we have compared the molecular mechanisms through which hyaluronan dodecasaccharides (HA12), and the known angiogenic factor, fibroblast growth factor 2 (FGF-2), ...

Cryptococcus neoformans causes life-threatening meningoencephalitis, particularly prevalent in AIDS patients. The interrelationship between C. neoformans and HIV-1 is intriguing, as both pathogens elicit severe neuropathological complications. We have previously demonstrated that the HIV-1 gp41 ectodomain fragments gp41-I33 (amino acids 579-611) and gp41-I90 (amino acids 550-639) can enhance C. ...

Regenerative medicine-based approaches for the repair of damaged cartilage rely on the ability to propagate cells while promoting their chondrogenic potential. Thus, conditions for cell expansion should be optimized through careful environmental control. Appropriate oxygen tension and cell expansion substrates and controllable bioreactor systems are probably critical for expansion and subsequent ...

OBJECTIVE: To assess the effect of intra-sphincteric injections of bone marrow mesenchymal stromal cells (MSCs) on Valsalva leak point pressure (VLPP) changes in an animal model of stress urinary incontinence (SUI). MATERIALS AND METHODS: Twenty-four female Sprague-Dawley rats underwent bilateral pudendal nerve section to induce SUI. Six rats were SUI controls, 6 received periurethral injection of ...

Osteopontin (OPN) and splice variants of CD44 (CD44(V)) have independently been identified as markers for tumor progression. In this study, we show that both OPN and CD44(V) are frequently overexpressed in human gastric cancer and that OPN-engaged CD44(V) ligation confers cells an increased survival mediated ...

The migration of polymorphonuclear leukocytes (PMNs) across the intestinal epithelium is a histopathological hallmark of many mucosal inflammatory diseases including inflammatory bowel disease. The terminal transmigration step is the detachment of PMNs from the apical surface of the epithelium and their subsequent release into the intestinal lumen. The current study sought to identify epithelial ...

Tumor progression requires a crosstalk with the tumor surrounding, where the tumor matrix plays an essential role. We recently reported that only the matrix delivered by a CD44v6-competent (ASML(wt)), but not that of a CD44v6-deficient (ASML-CD44v(kd)) rat pancreatic adenocarcinoma line supports metastasis formation. We here describe that this matrix ...

BackgroundEpigenetic inactivation of tumor suppressor genes (TSG) by promoter CpG island hypermethylation is a hallmark of cancer. To assay its extent in human lymphoma, methylation of 24 TSG was analyzed in lymphoma-derived cell lines as well as in patient samples.MethodsWe screened for TSG methylation using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in 40 ...

Work by our group and others has demonstrated a role for the extracellular matrix receptor CD44 and it's ligand hyaluronan in CD4+CD25+ regulatory T-cell (Treg) function. Herein we explore the mechanistic basis for this observation. Using mouse FoxP3/GFP+ Treg we find that CD44 co-stimulation promotes expression of FoxP3, in part through production of ...

The identification and separation of small intestinal epithelial stem cells are still on the preliminary stage. In this study, we planned to utilize immunohistochemistry, fluorescence-activated cell sorting (FACS) and RT-PCR to investigate the possibility of CD133 and CD44 as markers of human small intestinal epithelial stem cells. The expressions of CD133, ...

Protease-Activated Receptor-2 (PAR2) has been implicated through genetic knockout mice with cytokine regulation and arthritis development. Many studies have associated PAR2 with inflammatory conditions (arthritis, airways inflammation, IBD) and key events in tumor progression (angiogenesis, metastasis), but they have relied heavily on the use of single agonists to identify physiological roles for ...

Reduced cell-cell adhesion allows malignant epithelial cells to invade the basal membrane and penetrate the stroma. This implies the potential of the cells to escape from the primary tumor as well as spreading ability. Herein, we investigated the effects of leuprorelin acetate (LA), a GnRH agonistic analogue, alone or in combination with dihydrotestosterone (DHT), on the expression of molecules ...

Bone tissue engineering approaches increasingly focus on the use of mesenchymal stem cells (MSC). In most animal transplantation models MSC are isolated and expanded before auto cell transplantation which might be critical for clinical application in the future. Hence this study compares the potential of directly auto-transplanted versus in vitro expanded MSC with or without bone morphogenetic ...

We show here that IL-17-secreting CD4 T (Th)17 and CD8 T (Tc)17 effector cells are found in the lung following primary challenge with influenza A and that blocking Ab to IL-17 increases weight loss and reduces survival. Tc17 effectors can be generated in vitro using naive CD8 T cells from OT-I TCR-transgenic mice. T cell numbers expand 20-fold and a majority secretes IL-17, but little IFN-?. Many ...

The tumor cell-derived hyaluronidase (HAase) HYAL-1 degrades hyaluronic acid (HA) into proangiogenic fragments that support tumor progression. Although HYAL-1 is a critical determinant of tumor progression and a marker for cancer diagnosis and metastasis prediction, it has not been evaluated as a target for cancer therapy. Similarly, sulfated hyaluronic acid (sHA) has not been evaluated for ...

We have previously demonstrated that expression of the novel gene schlafen-3 (Slfn-3) correlates with intestinal epithelial cell differentiation (Patel VB, Yu Y, Das JK, Patel BB, Majumdar AP. Biochem Biophys Res Commun 388: 752-756, 2009). The present investigation was undertaken to examine whether Slfn-3 plays a role in regulating differentiation of FOLFOX-resistant (5-fluorouracil + ...

Exposure to ultraviolet (UV) irradiation has detrimental effects on skin accompanied by the increased metabolism of hyaluronan (HA), a linear polysaccharide important for the normal physiological functions of skin. In this study, the modulation of human keratinocyte response to UVB irradiation by HA (970 kDa) was investigated. Immortalized human keratinocytes (HaCaT) were ...

Metastatic progression is the cause of most cancer deaths. Host tumour cell separation (fission) is accompanied by simultaneous acquisition of migrating capability of cancer cells, remodeling of cellular architecture and effective 'homing' in body host environment. Cell remodeling involves cytoskeletal protein-protein and lipid-protein interaction together with altered ...

Okadaic acid-sensitive serine/threonine phosphatases have been shown to regulate interleukin-2 transcription and T-cell activation. Okadaic acid inhibits protein phosphatase 4 (PP4), a novel PP2A-related serine/threonine phosphatase, at a 50% inhibitory concentration (IC₅₀) comparable to that for PP2A. This raises the possibility that some cellular functions of PP2A, ...

A subgroup of patients with atopic eczema develops acute eczematous reactions to type I allergy-inducing agents such as pollen that clinically resemble type IV allergies induced by haptens like metal ions. To clarify the underlying immunologic mechanisms, this study was designed to map the inflammatory in situ topoproteome of eczematous responses to grass/birch pollen and nickel by using atopy ...

We undertook this study to characterize changes in the proliferative capacities, chondrogenic phenotypes, and gene expression profiles of human synovium-derived progenitor cells from osteoarthritic patients during in vitro expansion. Cells isolated from osteoarthritic synovia were cultured, and growth rates during serial passages were evaluated. Surface molecule expressions were determined by flow ...

We have demonstrated spontaneous development of autoimmune cholangitis, similar to human primary biliary cirrhosis, in mice expressing a dominant negative form of the transforming growth factor-? receptor (dnTGF-?RII) restricted to T cells. The autoimmune cholangitis appears to be mediated by autoreactive CD8⁺ T lymphocytes that home to the portal tracts and biliary system. ...

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Osteopontin, a secreted phosphoprotein, is a major modulator of the motility of several cell types including macrophages, osteoclasts and tumor cells. Through its interaction with integrins and CD44v, osteopontin can induce metalloprotease, inhibit apopto...

Osteopontin, a secreted phosphoprotein, is a major modulator of the motility of several cell types including macrophages, osteoclasts and tumor cells. Through its interaction with integrins and CD44v, osteopontin can induce metalloprotease, inhibit apopto...

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... Gelatinase-A, Cathepsin L Astrocytoma Hepatocyte growth factor/scatter factor, c-Met MTI-MMP, MT2-MMP ... Renal cancer Interleukin-6 receptor ...

CD44 is a multifunctional adhesion molecule that can undergo extensive alternative RNA splicing to generate multiple isoforms bearing different extracellular domains, a sub set of which have been correlated with metastasis in breast cancer. Three such exo...

... Abstract : Breast cancer stem cells exist in several breast cancer cell lines based on recognized surface marker CD44+/CD24 or low or Hoechst ...

Hyaluronan is a high molecular weight polyanionic polysaccharide that is increased in more advanced prostate cancers. Tumor cell interaction with this polysaccharide by specific receptors CD44 and RHAMM promote tumor growth, survival and invasion. Work du...

Our laboratory has recently devised two potential gene therapeutic approaches, the utilization of alternative splicing as a control element in the chimeric enzyme/prodrug therapy (CEPT), and dual modulation vectors. Both approaches aim at increasing the t...

... in several cancers [43]. In SW620 cells (human colon cancer cell line not expressing CD44), the motility of ... K., U. Rubenthiran, and S. Jothy. Motility of colon cancer cells: modulation by CD44 isoform...

Cancer is characterized by dysregulated growth control, overcoming of cellular aging, and metastasis formation. The latter distinguishes malignant tumors from benign tumors and is mediated by groups of molecules called homing receptors, cytokines, and pro...

Cancer is characterized by dysregulated growth control, overcoming of cellular aging, and metastasis formation. The latter distinguishes malignant tumors from benign tumors and is mediated by groups of molecules called homing receptors, cytokines, and pro...

CD44 is a widely expressed cell adhesion molecule that binds hyaluronan, an extracellular matrix glycosaminoglycan, in a tightly regulated manner. This regulated interaction has been implicated in inflammation and tumor metastasis. CD44 exists in the standard form, CD44H, ...

Successful repair after tissue injury and inflammation requires resolution of the inflammatory response and removal of extracellular matrix breakdown products. We have examined whether the cell-surface adhesion molecule and hyaluronan receptor CD44 plays a role in resolving lung inflammation. CD44-deficient mice ...

BACKGROUND: Molecular profiling of renal cell carcinomas (RCCs) may improve the distinction between oncocytoma and malignant RCC subtypes and aid in early detection of metastasis. The hyaluronic acid (HA) family includes HA synthases (HAS1, HAS2, HAS3), hyaluronidases (HYAL-1, HYAL-2, HYAL-3, HYAL-4, PH20, HYAL-P1), and HA receptors (CD44s, ...

of the thyroid. Clin Cancer Res 1999;5(10):2790�7. [PubMed: 10537343] 8. Fortin M.A. Salnikov A.V. Nestor M tissues (e.g., thyroid and prostate gland). CD44 binds to ECM and is associated with cell adhesion in epithelial tumors associated with a poor prognosis for cancer patients (5). U36, an anti-CD44v6 chimeric

Variant isoforms of the cell surface glycoprotein CD44 (CD44v) are expressed during development, in selected adult tissues and in certain metastatic tumor cells. CD44v differ from the standard isoform (CD44s) by up to ten additional ...

Abstract Elevated serum CD44, ICAM-1 and VCAM-1 have been linked to poor prognosis in aggressive lymphomas but their utility in low grade lymphomas remains undefined. We evaluated serum CD44, VCAM-1 and ICAM-1 levels in 100 patients with newly diagnosed indolent NHL. The median pre-treatment values of the markers ...