Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Splice variants of the glycoprotein CD44 are transiently expressed on lymphocytes during T cell activation. Increased expression of CD44v6 on peripheral blood lymphocytes (PBL) of patients with inflammatory bowel disease (IBD) was described recently. The aim of this study was therefore to characterize CD44v6 expression on CD4(+) lamina propria lymphocytes (LPL) of patients with active IBD in comparison to controls. CD44v6 expression on CD4(+) LPL (n = 19) of controls and patients with active IBD (Crohn's disease n = 14, ulcerative colitis n = 15) was analyzed by flow cytometry and compared to that on autologous PBL. Thereby, in vitro regulation of CD44v6 on LPL and PBL via CD3 and CD2 and the costimulatory signal B7-1 was examined. In addition, the role of protein kinase C (PKC) in CD44v6 expression was tested. CD44v6 expression was increased in CD4(+) LPL (median, 45%) compared to PBL (median, 38%). Surprisingly, in IBD CD44v6 was downregulated on CD4(+) lamina propria T cells, irrespective of their state of inflammation (median, 28%). CD44v6 expression on LPL was not upregulated upon CD3 activation alone but following costimulation with B7-1. However, CD2-mediated T cell activation sufficiently induced upregulation of CD44v6 on LPL and PBL. In our study, downregulation of CD44v6 on LPL of patients with IBD was not due to defective PKC activation. Taken together, these data indicate that decreased CD44v6 expression on LPL in IBD might be a feature of an inappropriate costimulatory signal in T cell activation.
Exp Mol Pathol 2001 Dec
PMID:Decreased CD44v6 expression in lamina propria lymphocytes of patients with inflammatory bowel disease. 1173 44

Experimental evidence suggests that attachment of ovarian carcinoma cells to the peritoneal mesothelium involves the interaction between CD44 on ovarian carcinoma cells and hyaluronic acid on mesothelial surfaces. The authors therefore evaluated local and disseminated ovarian serous carcinomas for the expression of standard CD44 and CD44 splice variants CD44v5, CD44v6, and CD44v7/8. The relative amount of hyaluronic acid (HA) in stroma surrounding tumor nests also was studied. Using immunohistochemistry and archival tissue, 14 serous ovarian carcinomas confined to the ovary (stage I) and 14 serous ovarian carcinomas with peritoneal implants and positive peritoneal fluid (stage III) were stained with antibodies to standard CD44, CD44v5, CD44v6, and CD44v7/8. All tissues also were analyzed for HA using a HA binding peptide. Immunostaining was classified as focal or diffuse and graded from 1 to 4 based on intensity. Immunoreactivity for standard CD44 was seen in 5 of 14 (36%) stage I tumors and 10 of 14 (71%) stage III tumors. Similarly, immunoreactivity with CD44v5 was seen in 2 of 14 (14%) stage I tumors and 9 of 14 stage III tumors (64%). Hyaluronic acid was present in the stroma surrounding all stage I and III tumors, but was more intense in the stroma adjacent to metastatic implants from stage III carcinomas. Tumor cells were uniformly negative for intracellular HA. These results suggest that CD44S and CD44v5 are differentially expressed in early (stage I) and advanced (stage III) ovarian serous carcinomas and support previous studies that suggest a role for CD44 and stromal HA in the dissemination of ovarian epithelial cancer.
Appl Immunohistochem Mol Morphol 2001 Dec
PMID:Expression of CD44S and CD44v5 is more common in stage III than in stage I serous ovarian carcinomas. 1175 56

In the present study we have compared the immunophenotypic characteristics of the CD56+lo and CD56+hi NK-cell subsets in a group of normal healthy adults. Our results show that CD56+hi NK-cells display greater light-scatter properties than CD56+lo NK-cells at the same time they have higher levels of CD25 and CD122 IL-2 chains, together with a higher reactivity for HLA-DR and CD45RO and lower levels of CD45RA, supporting that, as opposed to the majority of the CD56+lo population, CD56+hi NK-cells might correspond to a subset of activated circulating NK-lymphocytes. Higher expression of the CD2 and CD7 costimulatory molecules found for the CD56+hi NK-cells would support their greater ability to respond to various stimuli. In addition, CD56+hi NK-cells expressed higher levels of several adhesion molecules such as CD2, CD11c, CD44, CD56, and CD62L compared to CD56+lo NK-cells, supporting a particular ability of these cells to migrate from blood to tissues and/or a potential advantage to form conjugates with target cells. Interestingly, CD56+lo and CD56+hi NK-cells showed a different pattern of expression of killer receptors that might determine different activation requirements for each of these NK-cell subsets. For instance, absence or low levels of CD16 expression might explain the lower antibody-dependent cytotoxicity activity of CD56+hi NK-cells. On the other hand, the virtual absence of expression of the CD158a and NKB1 immunoglobulin-like and the greater reactivity for the CD94 lectin-like killer receptors on CD56+hi in comparison to CD56+lo NK-cells might determine different MHC-class I specificities for both NK-cell subsets, a possibility that deserves further studies to be confirmed.
Blood Cells Mol Dis
PMID:Immunophenotypic characterization of normal blood CD56+lo versus CD56+hi NK-cell subsets and its impact on the understanding of their tissue distribution and functional properties. 1177 57

Articular chondrocytes express the matrix receptors CD44 and integrins. Both of these receptors exhibit interactions with adjacent extracellular matrix macromolecules. In addition, both integrins and CD44 have the capacity for signal transduction as well as modulated interactions with the actin cytoskeleton. As such, both receptor families provide the chondrocytes a means to detect changes in matrix composition or to function as mechanotransducers. Disruption of CD44 or integrin-mediated cell-matrix interactions, either experimentally induced or when present in osteoarthritis, have profound effects on cartilage metabolism. Thus, CD44 and integrin receptors play a critical role in maintaining cartilage homeostasis.
Cell Mol Life Sci 2002 Jan
PMID:CD44 and integrin matrix receptors participate in cartilage homeostasis. 1184 31

Type I receptor tyrosine kinases, including the epidermal growth factor receptor (EGFR) and erbB2, have been implicated in mammary carcinoma growth and metastasis. Recent evidence suggests that type I receptor signaling may be mediated by the CD44 family of transmembrane glycoproteins that also have been implicated in mammary tumor progression. Here, the authors tested whether CD44, EGFR, and erbB2 interacted and colocalized with one another in four mammary carcinoma cell lines (MCF-7, MDA-MB-231, MDA-MB-435, and MDA-MB-436) and in cytology samples obtained from patients with metastatic breast cancer. CD44 constitutively colocalized and coimmunoprecipitated with erbB2 and EGFR in all four mammary carcinoma cell lines. CD44 also colocalized with erbB2 and EGFR in all cytology samples expressing erbB2. CD44 colocalized with EGFR in cells from only 1 of 16 erbB2-negative cytology samples. These data indicate that CD44-EGFR-erbB2 protein complexes occur in a high proportion of metastatic mammary carcinomas and suggest that CD44-type I receptor colocalization may be a novel prognostic marker for aggressive mammary cancers.
Appl Immunohistochem Mol Morphol 2002 Mar
PMID:CD44 associates with EGFR and erbB2 in metastasizing mammary carcinoma cells. 1189 33

Hyaluronan is a major glycosaminoglycan component of the extracellular matrix and CD44 is its principal ligand. In previous in vitro studies we have shown that CD44 and hyaluronan are involved in the invasive properties of the human breast cancer cell line Hs578T. The aim of this study was to test whether experimental therapy with hyaluronan interferes with tumor invasion and has an inhibitory effect on tumor growth in vivo. The Hs578T cell line was xenotransplanted orthotopically into the mammary fat pad of nu/nu mice. After tumor growth reached a maximum size of 5 x 5 mm, 50 microg of hyaluronan was injected intratumorally. The tumors of control nu/nu mice were injected with PBS. Four of 12 tumors from the hyaluronan-treated group regressed completely. This effect could be due to a saturation of the hyaluronan-binding sites on tumor cells or to an acceleration of tumor rejection by a non-T-cell-dependent mechanism. This study gives a rationale for future work on the antineoplastic effects of hyaluronan.
Exp Mol Pathol 2002 Jun
PMID:Effect of hyaluronan on xenotransplanted breast cancer. 1200 81

Barrett's adenocarcinoma currently shows the highest increase in the incidence of all malignant tumors. Reliable molecular markers to identify Barrett's patients at risk are still missing. Our own results demonstrate that the expression of CD44v6 correlates with the development of dysplasia in colorectal neoplasms. Therefore, we examined the expression of CD44 variants v5 and v6 in normal esophageal mucosa, non-dysplastic Barrett's mucosa, and Barrett's carcinoma. mRNA from biopsy specimens of patients with Barrett's esophagus (n = 19) or Barrett's carcinoma (n = 15) and patients without esophageal diseases (controls; n = 9) were extracted and used as templates for cDNA synthesis. CD44 variants were detected by RT-PCR with primers hybridizing with CD44 sequences up- and downstream of variable exons. CD44v6 expression was found in 36 of 56 biopsy specimens (64%) of non-dysplastic Barrett's mucosa, in 100% of squamous epithelium, and in none of the gastric mucosa specimens. Eleven of 15 specimens (73%) of Barrett's carcinoma tested positive for v6 expression. The identification of v5 expression did not give additional information. There was no correlation between CD44v5 or -v6 expression and staging or grading of the tumors. Expression of CD44v5 and -v6 seems to be independent of the development of cancer in Barrett's mucosa.
Exp Mol Pathol 2002 Jun
PMID:Expression of CD44v5 and -v6 in Barrett's carcinoma is not increased compared to that in nondysplastic Barrett's mucosa. 1200 84

There is growing evidence that immunocompetent cells are involved in the pathogenesis of chronic pancreatitis. Using a model of chronic pancreatitis induced by dibutyltin dichloride (DBTC) in rats, we have immunohistochemically phenotyped the infiltrating T lymphocytes, CD45RC+ cells, macrophages, as well as the IL-2 receptor as an activation marker during a time course of two months. In addition, the expression of CD44, of the integrin component CD18, and of MHC class II was determined. Furthermore, the isoforms of CD45 which are generated by alternative mRNA splicing were analysed using reverse transcription followed by the polymerase chain reaction-technique (RT-PCR). The pattern of the local leukocytes in the DBTC pancreatitis suggests that the acute unspecific inflammation is followed by an activation of T lymphocytes resulting in the chronic course of the disease.
Cell Mol Biol (Noisy-le-grand) 2002 May
PMID:Persistence of memory type lymphocytes in an experimental model of chronic pancreatitis in rats. 1203 Apr 36

Although a number of ATP-dependent RNA helicases are important for constitutive RNA splicing, no helicases have been implicated in alternative RNA splicing. Here, we show that the abundant DEAD-box RNA helicase p72, but not its close relative p68, affects the splicing of alternative exons containing AC-rich exon enhancer elements. The effect of p72 was tested by using mini-genes that undergo different types of alternative splicing. When the concentration of p72 was increased in transient transfections, the inclusion of enhancer-containing CD44 alternative exons v4 and v5 increased using a mini-gene that contained these exons and their flanking introns inserted into a beta-globin gene. Other types of alternative splicing were not impacted by altering p72 concentrations. Mutation of the p72 helicase ATP-binding site or deletion of the carboxy-terminal region of the protein reduced the ability of the transfected protein to affect CD44 variable exon splicing. Use of in vitro extracts overexpressing p72 indicated that p72 becomes associated with complexes containing precursor RNA. Helicases have been implicated both in altering RNA-RNA interactions and in remodeling RNA-protein complexes. CD44 exon v4 contains a potential internal secondary structure element that base pairs the 5' splice site with a region inside the exon located between enhancer elements. Mutations that destroyed this complementarity modestly increased inclusion in the absence of p72 but still responded to increasing p72 concentration like the wild-type exon, suggesting that p72 might have effects on protein-RNA interactions. In agreement with this hypothesis, p72 was not able to restore the inclusion of an exon mutated for its major enhancer element. Our results suggest that RNA helicases may be important alternative splicing regulatory factors.
Mol Cell Biol 2002 Aug
PMID:Regulation of alternative splicing by the ATP-dependent DEAD-box RNA helicase p72. 1213 82

The erbB2 receptor tyrosine kinase and the CD44 transmembrane glycoprotein interact with one another in numerous cell types. This interaction helps to maintain erbB2 activity that contributes to tumor progression. We investigated whether CD44 and erbB2 similarly interact in endometrial carcinomas in vitro and in situ. In contrast to other carcinomas, CD44 did not colocalize with erbB2 in any of the 51 cases of endometrial cancer analyzed. CD44 also did not coimmunoprecipitate or colocalize with erbB2 in two endometrial carcinoma cell lines. We propose that the lack of CD44-erbB2 interactions may reduce the contribution of erbB2 to endometrial carcinoma progression.
Appl Immunohistochem Mol Morphol 2002 Sep
PMID:Endometrial carcinoma cells are nonpermissive for CD44-erbB2 interactions. 1237 51


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