Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High level expression of the cell surface adhesion molecule CD44 standard form and its splice variants, have been causally linked to tumor metastasis. In this study, we investigated the significance of CD44 expression in human prostatic carcinoma cells. Immunocytochemistry showed high level expression of CD44 in cells from a high grade prostate tumor, and two androgen-independent, invasive prostatic carcinoma lines, PC-3 and TSU-Pr1. Normal prostatic epithelial cells and LNCaP, a low metastatic, androgen sensitive cell line, expressed none to a very low level of CD44, although mRNA transcripts were detected in all cell lines. Immunoprecipitation detected two proteins of M(r) approximately 140 kDa and 210 kDa in PC-3, and predominantly the M(r) approximately 95 kDa protein in TSU Pr1, but none in LNCaP. Most importantly, a neutralizing antibody to CD44 inhibited cell proliferation and basement membrane invasive activity, suggesting a definitive role of CD44 in prostate tumor growth and metastasis.
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PMID:Expression of CD44 in prostate cancer cells: association with cell proliferation and invasive potential. 754 62

There are several pieces of evidence suggesting a relationship between CD44 expression and tumor metastasis, but the role of CD44 in the metastatic processes is unclear. We analysed the role of CD44 in the experimental metastatic processes of B16BL6 melanoma cells using anti-CD44 monoclonal antibody (clone IM7). B16BL6 melanoma cells expressed CD44 and these cells treated with anti-CD44 monoclonal antibody increased in the experimental metastatic ability, indicating that CD44 participates in metastatic processes in B16BL6 cells. Furthermore, the adhesiveness of B16BL6 cells to endothelial cells and the retention of these cells in the lung increased by treatment with anti-CD44 monoclonal antibody. These results suggested that the CD44-mediated adhesion of tumor cells to endothelial cells was involved in the experimental metastatic process of B 16BL6 cells.
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PMID:CD44 participates in tumor cell adhesion to endothelial cells in the experimental metastatic process in B16BL6 melanoma cells. 754 63

The aim of this study was to compare the distribution of CD44 variants 5 and 6 in normal mucosa and gastric cancer and to determine their relationship with histoclinical Parameters of the disease. Experimental material included 112 paraffin blocks of various human gastric carcinomas. Both variants of CD44 were detected immunohistochemically with primary antibodies deriving from Bender Med. Systems. In normal gastric mucosa positive reactions with both antibodies were observed in surface epithelium, parietal cells, myocytes and vascular endothelia. They were also found in intestinal enterocytes, esophageal epithelium and myoepithelial. Additional reactivity with antibodies against variant 6 was observed in Paneth cells. In gastric cancer, variants 5 and 6 were demonstrated in 91% and 64% of cases respectively, without significant correlation with the tumor type. The occurrence of variant 6 correlated positively with tumor size (p = 0.081) and negatively with histological grading (p = 0.093). The relationship with metastases was insignificant.
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PMID:Immunohistochemical localization of CD44 variants 5 and 6 in human gastric mucosa and gastric cancer. 754 68

CD44 designates a large family of proteins generated from one gene by alternative splicing. Variants of CD44 (CD44v) differ from the standard form (CD44s) by usage of ten variant exons in various combinations. Some variants have been causally related to the metastatic spread of rat tumor cells. In human mammary carcinomas and colorectal carcinomas, the expression of CD44v has also been correlated with more progressed tumor stages. Moreover, the expression of CD44v on mammary and colorectal carcinomas correlates with a bad prognosis for patient survival. The biochemical features of these CD44 isoforms that may account for both their normal functions and their roles in tumor progression are discussed.
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PMID:CD44 isoforms in metastatic cancer. 754 77

Bone marrow plasma cells and stromal cells in multiple myeloma (MM) have been shown to be capable of releasing cytokines with angiogenic properties. Plasma cells can also express adhesion molecules controlling their adhesive interactions with endothelial cells. In the present study, we have evaluated by immunohistochemistry the extent of angiogenesis in the bone marrow of: a) 51 patients with active and non-active MM; b) 25 patients with monoclonal gammopathy of undetermined significance (MGUS). Plasma cells were investigated by flow cytometry for the expression of the adhesion molecules LFA-1, VLA-4, LAM-1, and CD44. The results showed that, while angiogenesis was very low or absent in patients with MGUS and non-active MM, it increased markedly in those with active MM. The highest detectability of plasma cell adhesion molecules, except LAM-1, was also found in these patients. The functional significance of these findings is unknown. Their consistent occurrence in the bone marrow of active myeloma patients, however, strongly suggests that more frequent adhesive interactions between plasma cells and their microvasculature underlie tumor dissemination.
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PMID:Bone marrow of patients with active multiple myeloma: angiogenesis and plasma cell adhesion molecules LFA-1, VLA-4, LAM-1, and CD44. 754 53

We have recently identified a new exon of the CD44 gene and demonstrated abnormal retention of a noncoding section, intron 9, in mRNA from bladder carcinomas. To analyze this further, the present study examined CD44 gene expression in cell lines from 14 esophageal, 3 colonic, and 4 breast carcinomas and in fresh samples from 20 colorectal carcinomas and corresponding normal colonic mucosa, using reverse transcriptase followed by the polymerase chain reaction (RT-PCR). This confirmed that there was abnormal assembly of several exons of the gene in cell lines and in tumor tissues from these organs. However, the most striking new finding was that intron 9 was present in RNA from 11 esophageal, 3 colon, and 1 breast carcinoma cell line, respectively. This was confirmed by RNase and DNase digestion analysis. Moreover, it was detected both in nuclear and cytoplasmic mRNA fractions, indicating that abnormal splicing of pre-mRNA occurs in cancer cells. The abnormal retention of intron 9 in CD44 gene transcripts was also demonstrated in tumor tissues from 16 (80%) of 20 patients with colon carcinoma, but there was no correlation with Dukes' stage. The biological significance of these observations is not yet understood. However, it is clear that, as with the abnormal expression pattern of CD44 variant exons, intron 9 retention is a good-candidate molecular diagnostic tool for colorectal carcinomas.
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PMID:Abnormal retention of intron 9 in CD44 gene transcripts in human gastrointestinal tumors. 754 38

CD44 is a polymorphic family of immunologically related cell surface proteoglycans and glycoproteins implicated in cell-cell and cell-matrix adhesion interactions, lymphocyte activation and homing, cell migration, and tumor metastasis. CD44 exists as a standard form and as multiple isoforms, each generated by alternative splicing of up to 10 variant exons (termed v1-v10) encoding parts of the extracellular domain. Using semiquantitative reverse transcriptase-PCR and Southern hybridization, alternative CD44 mRNA splicing was examined in 10 papillary thyroid carcinomas, 8 nodular goiters, 9 adenomas, 2 cases of thyroiditis, and 3 histologically normal thyroid controls. The amount of input cDNA for the CD44 PCRs was standardized against an internal control gene (glyceraldehyde phosphate dehydrogenase). Four papillary carcinomas showed significant overexpression of CD44 transcripts migrating between 750 and 1000 bp. These cases demonstrated reduced levels of the 482-bp standard isoform transcript. In six papillary cancers, we found a prominent v6-containing isoform at 750 bp that was present in only trace amounts in normal thyroid tissue. It is of interest that similar findings were seen in the majority of the goiters and adenomas but not in the cases of thyroiditis. These results show that deregulation of alternative CD44 splicing is a common feature of disordered thyroid follicular cell growth, both in neoplastic and nonneoplastic lesions. The data imply an important role for CD44, including CD44v6, in the pathogenesis of various thyroid lesions.
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PMID:Deregulated alternative splicing of CD44 messenger RNA transcripts in neoplastic and nonneoplastic lesions of the human thyroid. 755 35

CD44 is a polymorphic family of cell adhesion molecules that seems to be instrumental in the mechanism of tumor invasion and metastasis. Tumor cell expression of CD44, or lack thereof, may be one of the factors conditioning the highly disparate ability to penetrate the brain extracellular matrix (ECM) exhibited by glioblastoma multiforme (GM) and conventional meningioma. To assess the presence of CD44 in these two tumor types we have immunohistochemically investigated the expression of CD44 standard form (CD44s) and the variant isoforms containing the domain encoded by variant exon 3 (CD44v3) and variant exon 6 (CD44v6) in paraffin-embedded tissue from 10 conventional meningiomas and 10 GMs. A CD44s-/CD44v-phenotype was discerned in the meningioma cases, whereas GMs featured a CD44s+/CD44v- expression profile. Consequently, the growth patterns of meningioma and GM seem to be, at least in part, a reflection of their CD44 expression status. Paucity of CD44 in meningioma cells would render them unable to infiltrate the brain ECM, whereas CD44-rich glioma cells would successfully migrate through it. Conversely, lack of CD44v expression would contribute to explain the lack of metastatic potential characterizing both conventional meningioma and GM.
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PMID:Role of CD44 in the invasiveness of glioblastoma multiforme and the noninvasiveness of meningioma: an immunohistochemistry study. 755 49

CD44 is a transmembrane glycoprotein occurring in several isoforms with different extracellular regions. The various transcripts are encoded by one gene locus containing 20 exons, of which at least 10 can be alternatively spliced in nascent RNA. Isoforms encoded by the variant exons (termed CD44v) are highly restricted in their distribution in nonmalignant tissue as opposed to the standard form of CD44 (CD44s) abundant in many tissues. Specific variant isoforms containing exon 6v have been shown to render nonmetastatic rat tumor cells metastatic. Based on the prominent role in rat metastasis formation, CD44v isoforms were suggested to be involved in human tumor progression. Correlations between prognosis and expression of CD44v have been reported for gastric and colon carcinoma, for non-Hodgkin's lymphoma, and recently for breast carcinoma. We evaluated the expression of CD44 isoforms in node-positive (n = 119) and node-negative (n = 108) cases of breast carcinoma by immunohistochemistry using CD44v exon-specific mAbs. In a subset of 43 cases of high-risk patients, reverse transcription-PCR was used to determine the exon composition of the transcripts. Protein and RNA expression data were probed statistically for their correlation to survival of the patients and clinical risk factors. In contrast to recently published data (M. Kaufmann et al., Lancet, 345: 615-619, 1995), in our cohort disease-free and overall survival data did not indicate significant correlations with the expression of the analyzed isoforms in univariate and multivariate analyses. Comparison of CD44 protein expression with established clinical risk factors for survival such as tumor size (pT1+pT2) and histological grading revealed correlations with the presence of CD44s (P = 0.02 and P = 0.03, respectively) and CD44-9v (P = 0.05 for histological grading). Carcinoma tissues with elevated estrogen and progesterone receptor levels showed positive correlation with CD44-6v (P = 0.001), while a trend for significant coexpression of CD44s and CD44-9v isoforms was observed in estrogen receptor-positive tissues (P = 0.08 and 0.06, respectively). In breast cancer, CD44s, CD44-9v, and CD44-6v are apparently markers for cellular differentiation but not for tumor progression. Our data suggest that steroid hormone receptors may be associated with the in vivo expression of CD44-6v-containing isoforms in human mammary carcinoma.
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PMID:CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer. 758 12

Immunohistochemical screening of pancreatic adenocarcinomas from 24 different patients and 9 pancreatic carcinoma cell lines revealed variant CD44 expression in all specimens tested. In contrast to normal pancreatic tissue, carcinomas were strongly positive for epitopes encoded by variant exons v5, whereas v6 was expressed on carcinoma cells as well as normal ductal pancreatic cells. Analysis of RNA expression revealed clear differences between normal pancreatic tissue and tumor specimens. In normal pancreas, v6 and v3 solely and one major chain consisting of v6-v10 were expressed, whereas in pancreatic carcinoma, multiple splice variants were detected. In about 80% of all carcinoma cases and all cell lines tested, the exon v5 appeared in the chain containing at least v4-v10. These data thus far suggest that not the presence alone but the chain composition of the CD44 variant chains could be important for their altered function because one of the major differences between normal and cancer tissue is the linkage of CD44v5 to the CD44v6-containing chain.
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PMID:Differential expression of CD44 splice variants in human pancreatic adenocarcinoma and in normal pancreas. 758 21


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