Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CD44”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources
PubMed2004

Hyaluronan facilitates invasion of colon carcinoma cells in vitro via interaction with CD44.

Hyaluronan (HA) and its biosynthetic enzymes, HA synthases (HAS1, 2, and 3) are thought to participate in cancer progression. We have shown previously that HA production and HAS3 expression are increased in metastatic colon carcinoma cells (SW620) when compared with cells isolated from a primary tumor (SW480). Because invasion of the extracellular matrix is a fundamental event in tumor growth and metastasis, we hypothesized that SW620 cells would show greater invasive capability than SW480 cells, that invasion is HA dependent, and that HA mediates invasion via interaction with a cell-surface receptor. Invasion into artificial basement membrane (Matrigel) was assessed in vitro. To assess HA functionality, HAS expression was inhibited in SW620 cells by transfection with antisense HAS constructs. Decreased HA secretion and retention in the transfectants were confirmed using competitive binding and particle exclusion assays. SW620 cells demonstrated greater invasion through Matrigel than did SW480 cells. Antisense transfection decreased Matrigel invasion by SW620 cells by >60%; addition of exogenous HA restored invasion. Because the cell-surface HA receptor CD44 has been implicated in cancer progression, HA-CD44 interaction was then inhibited by incubation with an anti-CD44 antibody. Anti-CD44 antibody impaired invasion into Matrigel by 95%. Taken together, these data suggest that pericellular HA is critical for colon carcinoma cell invasion and that this invasive capability is dependent on interaction with CD44.

Binding, Competitive↗
PubMed2005

Functional proteomic screen identifies a modulating role for CD44 in death receptor-mediated apoptosis.

Apoptotic evasion is a hallmark of cancer and its resistance to chemotherapeutic drugs. Identification of cellular proteins that mediate apoptotic programs is a critical step toward the development of therapeutics aimed at overcoming apoptosis resistance. We developed an innovative high-throughput screen to identify proteins that modulate Fas ligand-mediated apoptosis using fluorophore-assisted light inactivation (HTS-FALIpop). The FALI protein knockdown strategy was coupled to a caspase activity assay with the ability to detect both proapoptotic and antiapoptotic surface molecules expressed by HT-1080 human fibrosarcoma cells. FALI of the Fas receptor (Fas/CD95) using a fluorescein-conjugated anti-Fas antibody abrogated Fas ligand-mediated caspase activation. Ninety-six single-chain variable fragment antibodies (scFv), selected for binding to the surface of HT-1080 cells, were screened by HTS-FALIpop. Three of the scFvs caused decreases in caspase induction after FALI of their protein targets. One of the targets of these positive scFvs was identified as CD44 and was validated by performing FALI using a CD44-specific monoclonal antibody, which resulted in similar protection from Fas apoptosis. CD44-targeted FALI was antiapoptotic in multiple human cancer cell lines, including both Fas signaling type I and II cells, and was also protective against other ligands of the tumor necrosis factor death receptor family. FALI of CD44 inhibited formation and activation of the death-inducing signaling complex, suggesting that CD44 regulates Fas at the cell surface. This mechanism of death receptor regulation represents a novel means of apoptosis modulation that could be exploited by pharmacologic agents.

Animals↗
PubMed2005

CD44 on LS174T colon carcinoma cells possesses E-selectin ligand activity.

Metastasis of circulating tumor cells requires a multistep cascade of events initiated by adhesion of tumor cells to the vascular endothelium of involved tissues. This process occurs under the forces of blood flow and is promoted by adhesion molecules specialized to interact under shear conditions. The endothelial molecule E-selectin is a major mediator of these adhesive events, and there is strong evidence that E-selectin receptor-ligand interactions contribute to the formation of metastasis. However, little is known about the identity of E-selectin ligand(s) expressed on cancer cells. To address this issue, we did SDS-PAGE analysis of membrane proteins, metabolic inhibition studies, and blot rolling assays of LS174T, a colon carcinoma cell line known to interact with E-selectin under physiologic flow conditions. Our studies show that LS174T cells express the hematopoietic cell E/L-selectin (HCELL) glycoform of CD44, which functions as a high-affinity E-selectin glycoprotein ligand on these cells. However, in contrast to the HCELL glycoform on human hematopoietic progenitor cells, which expresses carbohydrate-binding determinant(s) for E-selectin primarily on N-glycans of standard CD44, the relevant determinant(s) on LS174T cells is expressed on O-glycans and is predominantly found on variant isoforms of CD44 (CD44v). Our finding that tumor-associated CD44 splice variant(s) express E-selectin ligand activity provides novel perspectives on the biology of CD44 in cancer metastasis.

Adenocarcinoma↗
PubMed2005

CD44 expression is associated with increased survival in node-negative invasive breast carcinoma.

PURPOSE: CD44 is a multifunctional cell surface receptor with many known splice variants, some of which have been reported to play a role in tumor progression. The purpose of this study was to evaluate the prognostic significance of CD44 isoforms in early-stage, lymph node-negative invasive breast carcinoma. EXPERIMENTAL DESIGN: Immunohistochemical staining for CD44 isoforms was done on archival paraffin tissue sections of invasive breast carcinoma from a cohort of lymph node-negative patients who received no adjuvant tamoxifen or chemotherapy and who had a mean clinical follow-up period of 15 years. Immunohistochemical staining was done with antibodies to CD44s, the standard isoform of CD44, and to isoforms containing variant exon 6 (CD44v6); levels of staining were correlated with clinical outcome data. RESULTS: There was a trend towards increased disease-free survival for patients whose tumors had high anti-CD44s positivity (P = 0.05), and a significant association was observed between anti-CD44s positivity and disease-related survival (P = 0.04). Expression of CD44v6 isoforms did not correlate with clinical outcome. CONCLUSION: CD44 expression, as assessed by immunohistochemical staining with anti-CD44s, may be a favorable prognostic factor in patients with node-negative invasive breast carcinoma.

Adult↗
PubMed2006

Ischemia-induced renal expression of hyaluronan and CD44 in diabetic rats.

BACKGROUND/AIMS: Unilateral renal ischemia during 30 min causes severe, non-reversible renal damage in diabetic (DM) rats, but not in nondiabetic rats. Hyaluronan (HA) is a glycosaminglycan involved in various forms of renal injury. We examined the role of HA and CD44, a major receptor for HA, in the development of postischemic renal injury in DM rats. METHODS: The left renal artery of streptozotocin diabetic Wistar rats was clamped for 30 min. The HA content in the kidneys was measured. A biotinylated HA-binding probe was used to localize HA. Inflammatory cells and other cells expressing CD44 were identified by immunohistochemistry. RESULTS: In ischemic DM kidneys the renal HA-content started to increase already after 24 h and significantly so after 1-8 weeks after ischemia/reperfusion (I/R). The relative water content of the kidneys increased in parallel. HA started to appear in the cortex of ischemic DM kidneys 1 week after I/R. In contrast, the non-DM ischemic kidneys showed no increase of HA and water content after 1-8 weeks after I/R. The tubular cells in the cortex and outer medulla demonstrated increased staining for CD44. In the same compartments the increased numbers of infiltrating inflammatory cells also expressed CD44. CONCLUSION: HA-accumulation in the renal cortex might contribute to the renal damage seen after transient ischemia in DM rats by promoting inflammation through interaction between HA and CD44 expressing inflammatory cells. Furthermore, HA accumulation may contribute to an interstitial renal edema.

Animals↗
PubMed1995

Differential expression of CD44 in rabbit uterine epithelium during early pregnancy.

The expression of the cell surface glycoprotein CD44 was monitored in rabbit endometrium during early pregnancy and pseudopregnancy by immunohistochemistry. The epitope was not detected in the uterine epithelium of nonpregnant doses; in pseudopregnant animals it was expressed only weakly and late, most clearly detectable at the last stage investigated, i.e. on day 10. During pregnancy, however, CD44 was expressed more strongly in the epithelium starting on day 6, i.e. shortly before embryo implantation (day 7). Northern blot analysis confirmed this increase in expression. Immunohistochemically, CD44 expression peaked around days 8 and 9 of pregnancy and was generally localized on the lateral cell membranes of uterine epithelium, but not on basal or apical membranes. The staining pattern was similar on all major mucosal folds in that the signal was most intense in the luminalmost parts and slightly less in the middle of these folds. The intensity was gradually reduced towards the depth of the crypts with their deepest parts being negative. At day 10 of pregnancy the intensity of staining was clearly reduced in all parts of the epithelium that had been positive before. Fusion of epithelial cells, a characteristic phenomenon in pregnant rabbit uteri, which is particularly widespread in the implantation chamber, was accompanied with abolishment of CD44 expression. While stromal cells in general showed only a weak reaction, some individual cells in the stroma were always strongly positive (numbers increased after implantation). The trophoblast only occasionally exhibited some faint cellular staining in cytotrophoblast as well as in syncytiotrophoblast. These data show that CD44 is expressed in rabbit uterine epithelium during the periimplantation phase, and that its expression appears to be triggered by embryonic signalling and may be relevant for implantation.

Animals↗
PubMed1995

Differential expression and localization of integrins and CD44 in the membrane domains of human uterine epithelial cells during the menstrual cycle.

Human uterine epithelium displays a distinctly polarized organization with basal, lateral, and apical plasma membrane domains. Although nonadhesive throughout most of the menstrual cycle, uterine epithelial cells allow attachment of trophoblast cells to their apical pole during embryo implantation. Development of the receptive state might involve expression of cell adhesion molecules and/or redistribution of such molecules with respect to their localization at the basal, lateral, and apical membrane domains of cells. Expression and distribution of alpha 1-, alpha 3-, alpha 5-, alpha 6-, beta one-, beta 3- and beta 4-integrin subunits as well as of CD44 were examined in the luminal epithelium of human endometrium by immunohistochemistry in different phases of the menstrual cycle. The luminal epithelium was found to express alpha 1-, alpha 3-, alpha 6-, beta 1-, beta 4-integrin subunits and CD44. alpha l6-Integrin subunits and CD44 displayed cycle dependency. The alpha 6-integrin subunits were detected in the basal membrane domains in all phases. However, in correlation with increasing expression during the secretory phase of cycle, these subunits newly appeared in the lateral membranes of epithelial cells. CD44 showed increased expression in the secretory phase but was always restricted to the lateral membranes. The conspicuous behavior of alpha 6-integrin subunits and CD44 is discussed with respect to its possible functional significance for embryo implantation, and in relation to a hypothesis postulating that steroid-controlled master genes direct the acquisition of the receptive state of the luminal uterine epithelium by changing elements of the apicobasal polarity of these cells.

Endometrium↗
PubMed1994

Positive relationship between expression of CD44 and hepatic metastases in colorectal cancer.

This study was performed to determine the relationship between the expression of CD44, p53 and NM23 and the metastatic potential of colorectal cancer. Frozen sections of 56 cases of colorectal cancer were immunohistologically examined for the expression of CD44, p53 and NM23. Positive immunoreactivity was found in 30 of 56 cases (54%) in CD44, 26 of 56 (46%) in p53 and 20 of 56 in NM23 (36%), respectively. There was no significant relationship between the expression of these molecules and clinicopathological findings such as age, sex, size, location of tumor, histological type, serosal invasion, peritoneal dissemination, lymph node metastasis, extramural venous spread and tumor stage; however, when examining the relationship between the expression of these molecules and prognosis in terms of hepatic metastasis and recurrence after curative operation, a significant association was seen in the expression of CD44, but none in p53 and NM23. It was suggested that expression of CD44 could be used as a possible indicator to predict metastatic potential of colorectal cancer.

Antigens, Neoplasm↗
PubMedDate not supplied

Soluble CD44 variants in the serum of patients with urological malignancies.

In patients with malignant diseases, characteristic alterations in the expression of CD44 protein and their variants were found. For the present study, the serum concentrations of the standard isoform CD44 std and the two variant isoforms CD44 v5 amd CD44 v6 were measured by ELISA in patients with prostate cancer (n = 49), benign prostatic hyperplasia (n = 30), renal cell carcinoma (n = 31) and bladder cancer (n = 29). The data were compared with the results of 30 healthy men and 30 healthy women. The sCD44 v5 concentrations in patients with prostate cancer (p < 0.01), benign prostatic hyperplasia (p < 0.01) and men with renal cell cancer (p < 0.01) were significantly lower than those measured in the male control group. The sCD44 v5 concentrations observed in male patients with bladder cancer were lower than in the male control group (p < 0.05). Only in one group the concentration of sCD44 std differed significantly from the others. The sCD44 std concentration in male patients with renal cell cancer was significantly lower than in the male control group (p < 0.01). Other significant differences were not found. In contrast to results observed in other carcinomas, the determination of soluble CD44 proteins in serum cannot be recommended as a marker for urological malignancies.

Adult↗
PubMed1998

Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity.

Interactions between complementary receptors on leukocytes and endothelial cells play a central role in regulating extravasation from the blood and thereby affect both normal and pathologic inflammatory responses. CD44 on lymphocytes that has been "activated" to bind its principal ligand hyaluronate (HA) on endothelium can mediate the primary adhesion (rolling) of lymphocytes to vascular endothelial cells under conditions of physiologic shear stress, and this interaction is used for activated T cell extravasation into an inflamed site in vivo in mice (DeGrendele, H.C., P. Estess, L.J. Picker, and M.H. Siegelman. 1996. J. Exp. Med. 183:1119-1130. DeGrendele, H.D., P. Estess, and M.H. Siegelman. 1997. Science. 278:672-675. DeGrendele, H.C., P. Estess, and M.H. Siegelman. 1997. J. Immunol. 159: 2549-2553). Here, we have investigated the role of lymphocyte-borne-activated CD44 in the human and show that CD44-dependent primary adhesion is induced in human peripheral blood T cells through T cell receptor triggering. In addition, lymphocytes capable of CD44/HA-dependent rolling interactions can be found resident within inflamed tonsils. In analysis of peripheral bloods of patients from a pediatric rheumatology clinic, examining systemic lupus erythematosus, and a group of chronic arthropathies, expression of CD44-dependent primary adhesion strongly correlates with concurrent symptomatic disease, with 85% of samples from clinically active patients showing elevated levels of rolling activity (compared with only 4% of inactive patients). These rolling interactions are predominantly mediated by T cells. The results suggest that circulating T lymphocytes bearing activated CD44 are elevated under conditions of chronic inflammation and that these may represent a pathogenically important subpopulation of activated circulating cells that may provide a reliable marker for autoimmune or chronic inflammatory disease activity.

Adolescent↗
PubMed2003

RANTES (CCL5) uses the proteoglycan CD44 as an auxiliary receptor to mediate cellular activation signals and HIV-1 enhancement.

The CC-chemokine RANTES (regulated on activation normal T-cell expressed and secreted; CCL5) transduces multiple intracellular signals. Like all chemokines, it stimulates G protein-coupled receptor (GPCR) activity through interaction with its cognate chemokine receptor(s), but in addition also activates a GPCR-independent signaling pathway. Here, we show that the latter pathway is mediated by an interaction between RANTES and glycosaminoglycan chains of CD44. We provide evidence that this association, at both low, physiologically relevant, and higher, probably supraphysiologic concentrations of RANTES, induces the formation of a signaling complex composed of CD44, src kinases, and adapter molecules. This triggers the activation of the p44/42 mitogen-activated protein kinase (MAPK) pathway. By specifically reducing CD44 expression using RNA interference we were able to demonstrate that the p44/p42 MAPK activation by RANTES requires a high level of CD44 expression. As well as potently inhibiting the entry of CCR5 using HIV-1 strains, RANTES can enhance HIV-1 infectivity under certain experimental conditions. This enhancement process depends in part on the activation of p44/p42 MAPK. Here we show that silencing of CD44 in HeLa-CD4 cells prevents the activation of p44/p42 MAPK and leads to a substantial reduction in HIV-1 infectivity enhancement by RANTES.

Chemokine CCL5↗
PubMed2003

The spreading of B lymphocytes induced by CD44 cross-linking requires actin, tubulin, and vimentin rearrangements.

CD44 is a polymorphic family of adhesion molecules widely distributed on cells and tissues. CD44 is up-regulated on activated lymphocytes, and it can function as a receptor, mediating rolling and migration. Although it has been demonstrated that anti-CD44 antibodies bound to tissue-culture plates induce multidirectional emission of retractile dendrites ("spreading") in activated murine B lymphocytes, the involvement of cytoskeleton elements in this phenomenon is largely unknown. In this work, it is shown that the generation of dendrites induced by CD44 cross-linking in activated B cells depends on actin, microtubules, and vimentin reorganization. Immunofluorescence analysis showed that dendrite formation began with actin polymerization, and its extension was favored by microtubules and intermediate filaments of vimentin oriented to the polymerized actin. Pretreatment of activated B lymphocytes with cytochalasin E inhibited the dendrites formation; moreover, when cells were treated with this drug at different time points during the dendrite formation process, the stability of the dendrites was affected. In contrast, although the treatment with colchicine and nocodazole (tubulin polymerization inhibitors) inhibited the dendrites formation, it did not inhibit the initial phase of actin polymerization. According to these results, B cell spreading and dendrite formation induced by anti-CD44 antibodies require coordinated rearrangements of actin, microtubules, and vimentin, being the actin cytoskeleton, the most important element that confers stability and drives the morphological changes during B cell spreading, conceivably preparing B lymphocytes for locomotion.

Actins↗
PubMed1997

Neurofibromatosis 2 tumor suppressor protein colocalizes with ezrin and CD44 and associates with actin-containing cytoskeleton.

Neurofibromatosis 2 (NF2) protein (merlin; schwannomin) is a tumor suppressor involved in tumorigenesis of NF2-associated and sporadic schwannomas and meningiomas. The protein shares the domain structure of three homologous proteins: ezrin, radixin and moesin (ERM). ERM proteins function as membrane organizers and may act as linkers between plasma membrane molecules, such as CD44 and ICAM-2, and the cytoskeleton. We analyzed the distribution and effects of transfected NF2 protein in COS-1, CHO and 293 cells, and endogenous NF2 protein in U251 glioma cells. The distribution was compared to ezrin, CD44 and F-actin. Both transfected and endogenous NF2 protein localized underneath the plasma membrane in a pattern typical of an ERM protein. In COS-1 transfectants, NF2 protein typically codistributed with ezrin but, in cells with poorly developed actin cytoskeleton, it replaced ezrin in filopodia and ruffling edges. NF2 protein colocalized with CD44, which in transfected cells accumulated into restructured cell membrane protrusions. The association of CD44 and NF2 protein was further suggested by binding of CD44 from cellular lysates to recombinant NF2 protein. Interaction between NF2 protein and the actin-containing cytoskeleton was indicated by partial colocalization, by cytochalasin B-induced coclustering, and by retention of NF2 protein in the detergent-insoluble fraction. Transfected NF2 protein induced morphogenic changes. The cells contained restructured membrane extensions and blebs, and CHO cells expressing NF2 protein were more elongated than control transfectants. In conclusion, NF2 protein possesses functional properties of an ERM family member.

Actins↗
PubMed2004

Differential expression of CD44 during human prostate epithelial cell differentiation.

CD44 is a polymorphic transmembrane glycoprotein that binds hyaluronan and growth factors. Multiple isoforms of the protein can be generated by alternative splicing but little is known about the expression and function of these isoforms in normal development and differentiation. We have investigated the expression of CD44 during normal prostate epithelial cell differentiation. A conditionally immortalized prostate epithelial cell line, Pre2.8, was used as a model system. These cells proliferate at 33C but at 39C stop dividing and undergo changes consistent with early stages of cell differentiation. During the differentiation of these cells, the expression of the CD44 isoform v3-v10 was upregulated. Two layers of epithelial cells can clearly be distinguished in the human prostate, a basal layer expressing keratins 5/14 and a luminal layer expressing keratins 8/18. In prostate tissue the v3-v10 isoform was found predominantly in basal cells but also in keratin 14-negative, keratin 19-positive cells intermediate between the two layers. CD44 v3-v10 was also expressed in other keratin 14-negative prostate tissues, the ejaculatory ducts and prostatic urethra. Therefore, CD44 v3-v10 may be important as a cell surface marker for differentiating cells in the prostate epithelium.

Cell Differentiation↗
PubMed2000

Mobilization kinetics of CD34(+) cells in association with modulation of CD44 and CD31 expression during continuous intravenous administration of G-CSF in normal donors.

The aim of the present study is to evaluate the kinetics of CD34(+) cells and investigate the potential modulation of CD44 and CD31 expression on CD34(+) cells during continuous i.v. administration of G-CSF, thus to elucidate the possible mechanism of peripheral blood progenitor cell (PBPC) mobilization. Fifteen healthy donors were enrolled in this study. G-CSF (10 microg/kg/day) was administered for four consecutive days through continuous 24-h i.v. infusion. For measurement of complete blood counts, CD34(+) cell levels and their expression of CD44 and CD31, PB sampling was performed immediately before the administration of G-CSF (steady-state) and after 4, 8, 24, 48, 72, 96, and 120 h of G-CSF administration. The percentage and absolute number of CD34(+) cells significantly increased at day 3 (0. 55 +/- 0.09%, 51.12 +/- 24.83 x 10(3)/ml) and day 4 (0.47 +/- 0.09%, 46.66 +/- 24.93 x 10(3)/ml), compared to the steady-state level (0. 06 +/- 0.09%, 2.03 +/- 5.69 x 10(3)/ml). At day 3 to day 5 following the onset of G-CSF administration, a strong decrease of CD44 and CD31 expression was observed on mobilized CD34(+) cells compared to controls: the relative fluorescence intensity of CD44 and CD31 was, respectively, 50%-70% and 40%-90% lower than that of controls. We conclude that continuous i.v. administration of G-CSF apparently results in more rapid mobilization of CD34(+) cells, and downregulation of CD44 and CD31 on CD34(+) cells is likely to be involved in the mobilization of PBPC after treatment with G-CSF.

Adult↗
PubMed1996

Localization of glycosaminoglycans and CD44 in the human lacrimal gland.

Recent analyses of tears indicate the presence of glycosaminoglycans as their components, but their origin remains unknown. To further understand the origin of these tear components, we investigated by immunohistochemical techniques the localization of glycosaminoglycans and CD44 human lacrimal glands obtained from 20 cadavers at autopsy. Monoclonal antibodies to CD44, a receptor for hyaluronic acid, dermatan sulfate, chondroitin sulfate, and keratan sulfate were applied to the tissue. Hyaluronic acid binding region was also used for the staining of hyaluronic acid. By light microscopy, immunoreactivity for CD44 was mostly detected on the baso-lateral membrane of acinar and ductal cells, and the vascular endothelium in the interstitium. Positive staining of hyaluronic acid was associated intensely with the basal membrane of acinar and ductal cells and weakly, faintly or not at all with their lateral membrane. Positive staining of hyaluronic acid and immunoreactivity for dermatan sulfate were detected in interstitial fibrous structures; particularly, the former was intense in the perivascular fibrous structures, and the latter along the periparenchimal fibrous structures. Immunoreactivity for chondroitin sulfate and keratan sulfate was seen in some acinar cells and the acinar and ductal lumen. By electron microscopy, immunogold particles indication chondroitin sulfate sulfate or keratan sulfate labeled secretory granules of the acinar cells. Considering the fact that CD44 is a receptor molecule for hyaluronic acid, the association of hyaluronic acid with the basal membrane and weakly or faintly with the lateral membrane of acinar and ductal cells may be attributed to the expression of CD44 on the baso-lateral membrane of the cells. Moreover, the presence of immunoreactivity for chondroitin sulfate and keratan sulfate in secretory granules of acinar cells and their lumens suggests that tears from the lacrimal gland contain these glycosaminoglycans.

Chondroitin Sulfate Proteoglycans↗
PubMed1998

The role of CD44 as a cell surface hyaluronan receptor during tumor invasion of connective tissue.

Tumor progression involves a series of complex interactions between infiltrating malignant cells and adjacent normal tissues. The cell surface receptor CD44 has been implicated as an active participant in a number of these interactions. Although assigned a variety of functions, it is the role of CD44 as a receptor for the glycosaminoglycan hyaluronan that is likely to be of most importance. The matrix macromolecule hyaluronan often becomes deposited in the tissue spaces immediately surrounding invasive tumors. As such, hyaluronan may function as a ligand for CD44-mediated locomotion or assemble into a protective matrix coat surrounding the tumor cells. Alternatively, the adjacent hyaluronan-rich matrices may serve as a barrier to migration, breached in part by aggressive cell types exhibiting a capacity for CD44-mediated hyaluronan endocytosis. The significance of tumor-associated hyaluronan accumulation as well as potential functions of CD44--hyaluronan interactions are reviewed.

Animals↗
PubMed1998

Clinical implications of anomalous CD44 gene expression in neoplasia.

An intensive search continues for reliable markers that would be clinically useful in the diagnosis of small tumors and in the evaluation of their predicted clinical outcome. One potential marker, extensively studied in human samples is the cell surface adhesion molecule CD44. The single CD44 gene codes for a large family of cell surface proteins by alternative splicing and severe abnormalities have been observed in the patterns of its expression in many types of human tumors using both protein and RNA-based analyses. These abnormalities are manifested by markedly increased levels of unusual transcripts and proteins in tumor cells compared to the corresponding normal tissues. Aberrant processing of immature CD44 transcripts has also been observed in tumor cells and this can lead to the inappropriate retention of introns and to the use of cryptic splice sites in the mRNA. Inappropriate expression patterns of the alternatively spliced exons have also been linked both to tumor progression and to metastatic potential. The clinical relevance of all these observations is demonstrated by the frequent detection of these abnormalities in samples from malignant tumors of many different organs and by their presence in pre-invasive and high risk pre-cancerous lesions. This article reviews the current information regarding the expression of the CD44 gene in tumor cells and its potential use as a marker in clinical evaluation. The overall conclusion is that with the use of the latest assay techniques and perhaps in combination with other molecular markers, analysis of CD44 expression can provide new and powerful assays for the detection of neoplastic disease.

Animals↗