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At least 1,099 records · Page 61Linked to original sources
PubMed2000

Anti-interleukin-1 and anti-CD44 interventions producing significant inhibition of cartilage destruction in an in vitro model of cartilage invasion by rheumatoid arthritis synovial fibroblasts.

OBJECTIVE: To establish an in vitro model for the investigation of destructive processes in rheumatoid arthritis (RA), to study the interaction between fibroblasts, macrophages, and chondrocytes, and to evaluate strategies to inhibit joint destruction in RA. METHODS: Human and bovine chondrocytes cultured in sponges pretreated with native bovine embryonic extracellular matrix produced a cartilaginous matrix reflected by the incorporation of 35S into proteoglycans. The 3-dimensional culture system was optimized for the number of chondrocytes (10(5) cells/sponge), the timing of 35S incorporation (day 21 after chondrocyte isolation), and the medium (20% fetal calf serum). RA synovial fibroblasts (RASF; 10(5)) were added, and the matrix destruction mediated by these RASF was monitored by the release of 35S. The system was modulated by the addition of monocytes (U937 cells), cytokines (interleukin-1beta [IL-1beta] and tumor necrosis factor alpha [TNFalpha]), interleukin-1 receptor antagonist (IL-1Ra), and monoclonal antibodies against IL-1beta and CD44. RESULTS: RASF destroyed the bovine cartilaginous matrix within 2 weeks (days 5-12) and the human cartilaginous matrix within 3 weeks (days 10-18). Compared with the effect of RASF alone (mean +/- SD 948 +/-180 counts per minute/week), the addition of U937 cells (a monocytic cell line), IL-1beta, or TNFalpha to the incubation medium increased the destruction of human cartilaginous matrix by at least 71% up to 90% (ranging from 1,618+/-204 cpm/week to 1,802+/-307 cpm/week). IL-1Ra and anti-IL-1beta monoclonal antibodies reduced the destruction of human matrix by 45% and 35%, respectively; this was partially reversed by the addition of U937 cells. The pretreatment of RASF with anti-CD44 monoclonal antibody (an adhesion molecule and receptor for hyaluronic acid) inhibited the destruction of the cartilaginous matrix by an average of 41% over 3 weeks. CONCLUSION: This model is envisioned to study distinct aspects of human destructive joint diseases under in vitro conditions and to replace and/or supplement animal experiments in basic research and drug testing. Based on the fact that proinflammatory cytokines enhance destruction whereas IL-1Ra and antibodies against IL-1beta and CD44 inhibit the process, it is concluded that anti-IL-1- and anti-CD44-directed therapies may help prevent cartilage destruction in RA.

Animals↗
PubMed2001

Anti-Fas-induced apoptosis in chondrocytes reduced by hyaluronan: evidence for CD44 and CD54 (intercellular adhesion molecule 1) invovement.

OBJECTIVE: To investigate the in vitro effect of therapeutic hyaluronan (HA) of 500-730 kd on anti-Fas-induced apoptosis of chondrocytes from osteoarthritis (OA) patients, and to assess its mechanism of action by analyzing the role of the 2 HA receptors, CD44 and CD54 (intercellular adhesion molecule 1 [ICAM-1]). METHODS: Chondrocytes isolated from human OA knee cartilage were cultured and the effect of HA on both spontaneous and anti-Fas-induced apoptosis was evaluated. Apoptosis was analyzed by JAM test (for quantitative analysis of fragmented DNA), cell death detection immunoassay (for quantitative analysis of oligonucleosome), TUNEL assay, and electron microscopy. Blocking experiments with anti-CD44 and anti-CD54 alone or in combination were performed to investigate the HA mechanism of action. RESULTS: Both quantitative tests demonstrated that anti-Fas significantly induced apoptosis of isolated OA chondrocytes. HA at 1,000 microg/ml significantly reduced the anti-Fas-induced apoptosis of chondrocytes but did not affect spontaneous chondrocyte apoptosis. These data were also confirmed by TUNEL staining and by electron microscopy morphologic evaluation. The antiapoptotic effects of HA on anti-FAS-induced chondrocyte apoptosis were significantly decreased by both anti-CD44 (mean +/- SD 57 +/- 12% inhibition) and anti-ICAM-1 (31 +/- 22% inhibition). The mixture of the 2 antibodies had an additive effect, since the rate of inhibition increased to 87 +/- 13%. CONCLUSION: These data demonstrate that 500-730-kd HA exerts an antiapoptotic effect on anti-FAS-induced chondrocyte apoptosis by binding its specific receptors (CD44 and ICAM-1). Furthermore, this HA fraction may be able to slow down chondrocyte apoptosis in OA by regulating the processes of cartilage matrix degradation.

Aged↗
PubMed2006

Localization of CD44 and hyaluronan in the synovial membrane of the rat temporomandibular joint.

Previous studies have pointed out a lack of adhesion structures in the synovial lining layer of the rat temporomandibular joint (TMJ) despite showing an epithelial arrangement. CD44, a major cell adhesion molecule, plays crucial roles as an anchor between cells and extracellular matrices by binding hyaluronan (HA) for the development of organs or the metastasis of tumors. The present study examined the localization of CD44 in the synovial membrane of the rat TMJ by immunocytochemistry for OX50, ED1, and Hsp25, which are markers for the rat CD44, macrophage-like type A, and fibroblast-like type B synoviocytes, respectively. Histochemistry for HA-binding protein (HABP) was also employed for the detection of HA. OX50 immunoreactions were found along the cell surface and, in particular, accumulated along the surface of the articular cavity. Observations by a double immunostaining and immunoelectron microscopy revealed that all the OX50-immunopositive cells were categorized as fibroblastic type B cells, which had many caveolae and a few vesicles reactive to intense OX50. However, the macrophage-like type A cells did not have any OX50 immunoreaction in the synovial lining layer. A strong HABP reaction was discernable in the extracellular matrix surrounding both OX50-positive and -negative cells in the synovial lining layers, exhibiting a meshwork distribution, but weak in its sublining layer. This localization pattern of CD44 and HABP might be involved in the formation of the epithelial arrangement of the synovial lining layer. Furthermore, OX50 immunonegativity in the type A cells suggests their low phagocytotic activity in the rat TMJ under normal conditions.

Animals↗
PubMed1994

Expression of L-selectin, CD43, and CD44 in synovial fluid neutrophils from patients with inflammatory joint diseases. Evidence for a soluble form of L-selectin in synovial fluid.

OBJECTIVE: To study the expression of L-selectin, CD43, and CD44 on peripheral blood (PB) and synovial fluid (SF) neutrophils from patients with inflammatory joint diseases, and to investigate the presence of soluble L-selectin in both SF and plasma from patients with acute and chronic arthritis. METHODS: PB and SF neutrophils were isolated from 13 patients with rheumatoid arthritis (RA) and 17 patients with various inflammatory joint diseases other than RA. Expression of L-selectin, CD43, CD44, CD11a, and CD11b was determined in both unstimulated and in vitro-activated cells by immunofluorescence flow cytometry. Soluble L-selectin levels were estimated in SF and plasma by a semiquantitative radioimmunoassay. RESULTS: Neutrophils from SF showed diminished expression of L-selectin compared with PB neutrophils; CD43 expression and CD44 expression were decreased in SF neutrophils from most patients. In contrast, SF neutrophils exhibited significantly increased expression of CD11b, to an extent similar to that seen with in vitro-activated PB neutrophils. Soluble L-selectin was detected at similar levels in SF and PB. CONCLUSION: The phenotypic profile of SF neutrophils (low levels of L-selectin, CD43, and CD44, and high levels of CD11b) from most patients with RA or other inflammatory joint conditions resembles that observed in in vitro-activated neutrophils. Our results suggest that SF neutrophils are activated to a similar degree in inflammatory joint diseases with different pathogenic mechanisms.

Acute Disease↗
PubMed2006

The accumulation of intracellular ITEGE and DIPEN neoepitopes in bovine articular chondrocytes is mediated by CD44 internalization of hyaluronan.

OBJECTIVE: A dramatic loss of aggrecan proteoglycan from cartilage is associated with osteoarthritis. The fate of residual G1 domains of aggrecan is unknown, but inefficient turnover of these domains may impede subsequent repair and retention of newly synthesized aggrecan. Thus, the objective of this study was to determine whether ITEGE- and DIPEN-containing G1 domains, generated in situ, are internalized by articular chondrocytes, and whether these events are dependent on hyaluronan (HA) and its receptor, CD44. METHODS: ITEGE and DIPEN neoepitopes were detected by immunofluorescence staining of bovine articular cartilage chondrocytes treated with or without interleukin-1alpha (IL-1alpha). Additionally, purified ITEGE- or DIPEN-containing G1 domains were aggregated with HA and then added to articular chondrocytes, articular chondrocytes transfected with CD44delta67, or COS-7 cells transfected with or without full-length CD44. Internalized epitopes were distinguished by their resistance to extensive trypsinization of the cell surface. RESULTS: Both ITEGE and DIPEN were visualized within the extracellular cell-associated matrix of chondrocytes as well as within intracellular vesicles. Following trypsinization, the intracellular accumulation of both epitopes was clearly visible. IL-1 treatment increased extracellular as well as intracellular ITEGE epitope accumulation. Once internalized, the ITEGE neoepitope became localized within the nucleus and displayed little colocalization with HA, DIPEN, or other G1 domain epitopes. The internalization of both ITEGE and DIPEN G1 domains was dependent on the presence of HA and CD44. CONCLUSION: One important mechanism for the elimination of residual G1 domains following extracellular degradation of aggrecan is CD44-mediated co-internalization with HA.

Aggrecans↗
PubMed1995

Expression of cell interaction molecules by immature rat thymocytes during passage through the CD4+8+ compartment: developmental regulation and induction by T cell receptor engagement of CD2, CD5, CD28, CD11a, CD44 and CD53.

Rat thymocytes of the T cell receptorlow (TcRlow) CD4+8+ subset which is the target of repertoire selection are heterogeneous with respect to expression of the cell interaction (CI) molecules CD2, CD5, CD11a/CD18 (LFA-1), CD28 and CD44. We show that this heterogeneity is due to the developmental regulation of these CI molecules during passage through the CD4+8+ compartment, and to up-regulation by TcR engagement. Thus, cohorts of CD4+8+ cells differentiating synchronously in vitro from their direct precursors, the immature CD4-8+ cells, were homogeneous with regard to CI molecule expression. Upon entry into the CD4+8+ compartment, they expressed relatively high levels of CD2 and CD44, and moderate levels of CD5, CD28 and CD11a. CD2, CD28 and CD44 were slightly down-regulated during the following 2 days, whereas CD5 slightly increased and CD11a remained constant. TcR stimulation using immobilized monoclonal antibodies resulted in rapid and dramatic up-regulation of CD2, CD5 and CD28 and, to a lesser extent, of CD11a and CD44. Finally CD53, a triggering structure absent from unstimulated CD4+8+ thymocytes was also rapidly induced by TcR stimulation. Inclusion of interleukin (IL)-2, IL-4, or IL-7 in this in vitro differentiation system did not affect the levels of CI molecules studied. Since the high levels of CI molecules induced by TcR-stimulation correspond to those found in vivo on TcRintermediate thymocytes known to be undergoing repertoire selection, these results suggest that upregulation of CI molecules by TcR engagement provides a mechanism by which thymocytes that have entered the selection process gain preferential access to further interactions with stromal and lymphoid cells in the thymus.

Animals↗
PubMed2004

CD44-independent hepatocyte growth factor/c-Met autocrine loop promotes malignant peripheral nerve sheath tumor cell invasion in vitro.

Malignant peripheral nerve sheath tumors (MPNSTs) are invasive peripheral nerve neoplasms that express both the receptor tyrosine kinase c-Met and its ligand hepatocyte growth factor (HGF). The combined expression of these proteins has been implicated in tumor cell growth and metastasis. However, HGF/c-Met autocrine activity requires the presence of a serine protease, the HGF activator (HGFA), and, in some cells, the CD44 transmembrane glycoprotein. Here, we found that HGFA, HGF, c-Met, and CD44 are coexpressed in MPNSTs but their localization did not correlate with increased cell proliferation. The ST8814 MPNST cell line also expresses all of these proteins, can convert pro-HGF to active HGF, and exhibits constitutive c-Met phosphorylation. Blocking c-Met activity or expression inhibits the invasive behavior of these cells but not their proliferation. Interestingly, although a CD44 splice variant contributes to MPNST cell invasion and interacts with c-Met and HGF in ST8814 cells, it is not required for c-Met activation. These data indicate that an HGF/c-Met autocrine loop can promote MPNST invasion through a CD44-independent mechanism and suggest that c-Met, HGFA, and HGF are potential molecular targets to inhibit MPNST metastasis.

Autocrine Communication↗
PubMed1998

Expression of E-cadherin, alpha-catenin, beta-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: an immunohistochemical study.

Immunolocalization of E-cadherin (E-cad), alpha-catenin, beta-catenin, and CD44 has rarely been investigated in human cholangiocarcinoma (CC). We, therefore, immunohistochemically examined the expression of E-cad, alpha-catenin, beta-catenin, CD44 standard (CD44s), and CD44 variants (CD44v) including CD44v5, CD44v6, CD44v7-8, and CD44v10 in normal adult livers and in 47 cases of CC; and the results were then correlated with tumor grade, vascular invasion, metastasis, p53 expression, proliferative fraction (Ki-67 labeling), and c-erbB2 expression. In normal livers, E-cad, alpha-catenin and beta-catenin, but not CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10, were expressed at the cell membrane of normal intrahepatic bile ducts. In CC, membranous expression of E-cad, alpha-catenin, and beta-catenin was the same or reduced when compared with non-cancerous bile ducts in the majority of CC. We found that the down-regulation of E-cad, alpha-catenin, and beta-catenin expression significantly correlated with tumor high grade, but not with vascular invasion, metastasis, p53 expression, Ki-67 labeling, or c-erbB2 expression, except for beta-catenin, the down-regulation of which was associated with c-erbB2 down-regulation. CD44s, CD44v5, CD44v6, CD44v7-8 and CD44v10 were frequently expressed at the membrane of CC cells. There were, however, no significant correlations between these aberrant CD44 expression and tumor grade, metastasis, vascular invasion, p53 expression, Ki-67 labeling, or c-erbB2 expression, with a few exceptions of CD44s and CD44v5. We found that CD44s aberrant expression significantly correlated with absence of metastasis and vascular invasion, and that CD44v5 aberrant expression significantly correlated with p53 under-expression. These results suggest that membranous expression of E-cad, alpha-catenin, and beta-catenin is reduced in a majority of CC and this down-regulation correlates with CC high grade, and that beta-catenin down-regulation is associated with c-erbB2 down-regulation. The data also suggested that CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10 may be neoexpressed during carcinogenesis of CC but this neoexpression does not correlate with tumor progression in CC, with the exception of CD44s and CD44v5.

Adult↗
PubMed1995

Glycoconjugate profile and CD44 expression in human melanoma cell lines with different metastatic capacity.

Changes in glycoconjugate production have been reported for tumor cells. In this study, we investigated the glycoconjugate expression pattern in normal human melanocytes and in a panel of 6 human melanoma cell lines with different metastatic capacity after s.c. inoculation into nude mice. Glycoconjugates were labeled in vitro with [35S] sulphate and [3H] glucosamine, purified from cells and culture medium by column chromatography and identified by treatment with specific glycosidases. Characterization of the purified glycoconjugate fractions as well as alcian-blue staining of xenograft lesions revealed that hyaluronic acid (HA) is the main glycoconjugate produced by all cell lines. Highly metastatic cell lines expressed higher levels of HA than melanocytes and than weakly metastatic or non-metastatic cell lines. In addition, a shift in dominance from chondroitin-sulphate proteoglycan to heparan-sulphate proteoglycan was observed with increasing metastatic capacity. We also studied the expression and binding activity of the HA receptor CD44. Immunoprecipitation experiments indicated high CD44 synthesis only in highly metastatic cell lines, but FACS analysis demonstrated approximately the same surface expression in melanocytes as in all cell lines. Adhesion assays to immobilized HA showed that CD44 can be present in an inactive or an active conformation. Our data suggest that a combination of increased HA production and the expression of CD44 on the cell surface may be associated with high metastatic potential of human melanoma cell lines in nude mice.

Animals↗
PubMed1995

CD44 expression patterns in breast and colon tumors: a PCR-based study of splice variants.

CD44 cell-surface receptor expresses multiple isoforms, some of which are believed to play a role in tumor growth and metastasis. The CD44 gene is composed of 19 exons, of which 9 (exons 6 to 14) are alternatively spliced to form inclusions in the intervening membrane proximal region. Sequences present in the shortest metastatic variant cloned from a rat metastatic cell line have been shown to correspond to human exons 10 and 11, also called exons v6 and v7. Using RT-PCR, we have addressed in detail the CD44 isoforms produced in human breast and colon tumors. We analyzed 53 breast-tumor- and 58 colon-tumor-related samples as well as 1 benign mastopathy, 1 normal breast, 4 non-invaded lymph nodes and 8 normal colon tissues. All tumors analyzed expressed the hemopoietic CD44 (CD44H) isoform (no alternatively spliced exons added), whereas 81% expressed the CD44E form (addition exons 12, 13 and 14). Furthermore, 85% of tumors presented complex patterns of expression, with an average number of 5 to 6 bands detected. In view of their implication in the metastatic process, we investigated in greater detail the isoforms containing exons 10 and 11 (v6 and v7). Exon 10 was more frequently expressed than exon 11, 80% and 57% of the samples respectively. The great majority of cases showed ladder-like patterns starting from the shortest forms (exons 5-10 or 5-10-11) and larger-molecular-weight bands corresponding predominantly to sequential inclusions of exons from 3' to 5'. Exon-10 and exon-11 variants were also found in one benign mastopathy. The majority of normal tissues (1 breast and 6/8 colon) expressed only the CD44H isoform. These data indicate that expression of metastatic variants is common in human breast and colon tumors and can occur early during cancer progression, as testified by their presence in a benign breast tumor. While expression of exon-10 variants were correlated with presence of distal metastases in colon tumors, exon-11 variants were not (metastatic events were too rare in our breast-tumor series to reach significance). This suggest that exon 10 may correspond to the minimal sequences required to favor metastatic events.

Alternative Splicing↗
PubMed1991

The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate-bearing cells.

CD44 is a polymorphic integral membrane protein which recognizes hyaluronate and whose proposed roles encompass lymphocyte activation, matrix adhesion and the attachment of lymphocytes to lymph node high endothelial venules (HEVs). Immunochemical and RNA blot data have supported the existence of two forms of CD44: a hematopoietic form expressed by cells of mesodermal origin (and by some carcinoma cell lines) and an epithelial form weakly expressed by normal epithelium but highly expressed by carcinomas. This report describes the isolation of a cDNA encoding a distinct CD44 polypeptide expressed by epithelial cells. Re-expression of each form of CD44 in a B cell line allowed cells transfected with the hematopoietic but not the epithelial form to bind to viable rat lymph node HEV cells in primary culture.

Amino Acid Sequence↗
PubMed2006

Effects of CD44 antibody-- or RGDS peptide--immobilized magnetic beads on cell proliferation and chondrogenesis of mesenchymal stem cells.

We evaluated the efficacy of a novel mesenchymal stem cell (MSC) delivery system using an external magnetic field for cartilage repair in vitro. MSCs were isolated from the bone marrow of Sprague Drawley rats and expanded in a monolayer. To use the MSC delivery system, two types of MSC-magnetic bead complexes were designed and compared. Expanded MSCs were combined with small-sized (diameter: 310 nm) carboxyl group-combined (0.01-0.04 micromol/mg) magnetic beads, Ferri Sphere 100C, through either anti-rat CD44 mouse monoclonal antibodies or a synthetic cell adhesion factor, arginine (R)-glycine (G)-aspartic acid (D)-serine (S) (RGDS) peptide. Both cell complexes were successfully created, and were able to proliferate in monolayer culture up to at least day 7 after separation of magnetic beads from the cell surface, although the proliferation of the complexes was slower in the early period of culture than that of non-labeled rat MSCs (after 7 days of culture: proliferation of CD44 antibody-bead complexes, approximately 50%; RGDS peptide-bead complexes, 70% versus non-labeled rat MSCs, respectively). These complexes were seeded onto culture plates with or without an external magnetic force (magnetic flux density was 0.20 Tesla at a distance of 2 mm from plate base) generated by a neodymium magnet, and supplemented with chondrogenic differentiation medium. Both complexes could be attached and gathered effectively under the influence of the external magnet, and CD44-bead complexes could effectively generate chondrogenic matrix in monolayer culture. In a three-dimensional culture system, the production of a dense chondrogenic matrix and the expression of type II collagen and aggrecan mRNA were detected in both complexes, and the chondrogenic potential of these complexes was only a little less than that of rat MSCs alone. Thus, we conclude that due to the fact that MSC-RGDS peptide-bead complexes are composed using a biodegradable material, RGDS peptide, as a mediator, the RGDS peptide-bead complex is more useful for minimally invasive clinical applications using our design of magnetic MSC delivery system than CD44 antibody-beads.

Animals↗
PubMed1991

CD10 and CD44 genes of leukemic cells and malignant cell lines show no evidence of transformation-related alterations.

The expression of CD10/CALLA is associated primarily with childhood leukemia of pre-B lymphocyte phenotype. We have compared the hybridization pattern of the CALLA gene from leukemic and normal cells digested with several restriction enzymes. No alterations were noticed with Eco RI, Sac I, Pvu II, Eco RV, Hind III, and Msp I. Since CALLA is also found on other malignancies, we analyzed DNA samples prepared from cell lines derived from leukemia, lymphoma, glioblastoma, retinoblastoma, and neuroblastoma. Normal restriction patterns were observed for all the lines regardless of their CALLA phenotype. Having demonstrated previously that CALLA was structurally identical to neutral endopeptidase 3.4.24.11 (NEP), we have now established a correlation between surface expression of CALLA and NEP activity on leukemia samples and on several cell lines. Malignant cells tested expressed a functionally active enzyme and no gross alteration was present in the CALLA gene. The CD44 gene is expressed on most cells of hemopoietic origin and on greater than 95% of cases of acute lymphoblastic leukemia and acute myeloblastic leukemia studied. It is also expressed on normal astrocytes and on malignant cells of glioma/astrocytoma types. We now report that a similar pattern of hybridization was observed with Sac I, Pvu II, and Eco RI for leukemic samples, normal cells, and malignant cell lines. A polymorphism was recently detected for CD44 using Hind III; leukemic cells and malignant lines also showed this normal polymorphism. Thus no deletion or insertion could be detected in the CD44 gene of leukemic cells and malignant lines, suggesting that no gross DNA alterations were involved. The correlation between surface expression and enzymatic activity of CD10/CALLA and the expression of CD44 on a variety of malignant cells would suggest that the structure and function of these two gene products are probably not altered by the process of transformation.

Antigens, CD↗
PubMed1999

Activation and interaction of CD44 and hyaluronan in immunological systems.

Adhesive interactions between receptors on vascular endothelial cells (EC) and circulating leukocytes are pivotal in regulating leukocyte extravasation. Although primary adhesion of lymphocytes to EC has been primarily attributed to the selectin family of receptors, CD44 can also mediate this function when activated to bind its ligand hyaluronan (HA). Triggering through the T cell receptor induces activated CD44 and CD44-dependent primary adhesion in both human and mouse lymphocytes, and the interaction can mediate the extravasation of activated T cells into an inflamed site. Lymphocytes capable of CD44/HA-dependent primary adhesion are found in peripheral blood of some rheumatologic patients, and their presence is associated with concurrent symptomatic or active disease. Thus, circulating T cells bearing activated CD44 may represent a pathogenically important subpopulation of activated cells that is elevated under conditions of chronic inflammation. Together, these data add to the selectin and immunoglobulin gene families a new receptor/ ligand pair and further our understanding of their potential physiological role; i.e., antigen-specific T cell activation together with local vascular inflammation permits the CD44/HA interaction and subsequent T cell extravasation.

Animals↗
PubMed2002

CD44 expression in human gliomas.

BACKGROUND AND OBJECTIVES: Glioma invasiveness involves the attachment of tumor cells to the brain extracellular matrix, rich in hyaluronic acid (HA). CD44, the principal receptor for HA is found as a standard molecule (CD44s) or as variants (CD44v). We undertook a retrospective study to evaluate the expression pattern of CD44s, the isoforms CD44v3, v4/5 and v6 and to correlate their expression with clinical-anatomopathological parameters and survival rate. METHODS: The expression of these molecules was evaluated immunohistochemically in 84 gliomas. RESULTS: No expression of CD44v was detected in any tumors. CD44s staining of tumor cells was found in 70 of 84 (83.3%) of the gliomas. In 23 of 39 (59.0%) of the GBM more than the 70% of the cells were stained, while only 2 of 21 (9.5%) of LGA showed high expression. The association between CD44 and histological grade remained when the prognostic variables were considered in a multivariate analysis. Higher expression of CD44 was associated with worse overall survival rate; however, the Cox analysis indicated that survival was not associated with CD44. CONCLUSIONS: Our results suggest that overexpression of CD44s could be relevant in determining the highly invasive behaviour of gliomas, though it does not behave as an independent prognostic factor for survival.

Adolescent↗
PubMed2003

Hypermethylation of GSTP1, CD44, and E-cadherin genes in prostate cancer among US Blacks and Whites.

BACKGROUND: In the US, the incidence and mortality of prostate cancer is about twofold higher among US Blacks compared to Whites, suggesting racial differences in prostate tumor occurrence and aggressiveness. The reason for these racial differences is unknown. Epigenetic events such as promoter-region gene hypermethylation may be influenced by environmental exposures and have been implicated in prostate carcinogenesis (by the silencing of tumor suppressors and other regulatory genes). METHODS: Using real-time methylation-sensitive PCR, we assessed differences in DNA hypermethylation of GSTP1, CD44, and E-cadherin (three genes thought to be important in the progression of prostate cancer) in archival tumor tissue of black (n = 47) and white men (n = 64). RESULTS: We found a high prevalence of GSTP1 hypermethylation overall (84%) but no differences by race (89 and 83% in black vs. white men, respectively), tumor stage, or grade. Although CD44 hypermethylation was less prevalent overall (found in 32% of tumors), we observed a 1.7-fold higher frequency among black men (43 vs. 25% in black vs. white men, P = 0.05) and a correlation with tumor grade (CD44 was hypermethylated in 10, 42, and 52% of well, moderate, and poorly differentiated tumors, respectively, P = 0.003) but not disease stage. The E-cadherin gene was not hypermethylated in any of the tumors. In summary, of the three genes examined, only CD44 hypermethylation differed by race and correlated with tumor grade, independent of race. CONCLUSIONS: These preliminary findings suggest that differences in gene promoter hypermethylation may potentially underlie racial differences in prostate cancer pathogenesis and should be explored in larger studies.

Aged↗
PubMed1998

Shedding of CD44 from PMA-differentiated U-937 cells is enhanced by treatment with mineral particles.

In this report, we show that enhanced shedding of CD44 might contribute to the down-regulation of this receptor observed after phagocytosis of MnO2 particles by PMA-differentiated U-937. The apparent Mr of the soluble CD44 detected in culture supernatants was slightly lower than that of the membrane form suggesting that shedding resulted from proteolytic cleavage. Increased shedding of CD44 was also noted with other mineral particles (chrysotile and DQ12) but to a lower extent whereas some (TiO2 and amosite) had no effect on this process. These results indicate that shedding enhancement was particle-specific rather than a general consequence of phagocytosis. The ability of the particles to enhance CD44 shedding was not directly dependent on their cytotoxic potency. Different patterns of reactivity were noted with CD11b, suggesting that the underlying mechanisms are specific.

Asbestos↗
PubMed1999

Heparan sulfate composition of alternatively spliced CD44 fusion proteins.

Prior analyses of recombinant CD44 fusion proteins have indicated that combinatorial splicing of variant exons exerts distal effects on chondroitin sulfate content and structure, which may regulate the biological properties of the respective CD44 isoforms. The consequences of splicing of variant exons V4-7 on the heparan sulfate moieties were therefore examined, utilizing recombinant chimeras containing exons V3 and V8-10, engineered with or without exons V4-7 and expressed as Ig fusion proteins in COS cells. Splicing of exons V4-7, though they contain no consensus motifs for glycosaminoglycan assembly, resulted in markedly increased polymer sulfation levels of the heparan sulfates. The sulfate groups of both the CD44 V3-10 and V3,8-10 isoforms occurred as di- and tri-sulfated dissacharide units and were restricted to one N-sulfated block domain within the polymers. Compared to native human keratinocyte CD44, the recombinant heparan sulfates were relatively low in sulfate content. Our data indicate that variant exon V4-7 splicing exerts distal effects on the composition of this glycosaminoglycan. These effects may regulate those functions that are mediated through the heparan sulfate moieties, such as the binding of growth factors.

Alternative Splicing↗