Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD44 is an integral membrane glycoprotein that is a principal receptor for hyaluronan and plays a role in cell-extracellular matrix interactions. Recent studies of melanomas in mouse models have suggested that increased CD44 expression by these tumors may relate to metastatic potential. Immunohistochemical expression of CD44 (standard [s] and variant [v6]) in benign and malignant nevomelanocytic lesions was assessed in formalin-fixed, paraffin-embedded tissue and was correlated with histological parameters and prognostic factors. Cases included benign nevi (three junctional, four compound, five intradermal, five blue, six Spitz, one deep penetrating), architecturally disordered (dysplastic) nevi (three, and primary (22) and metastatic melanomas (eight). All of the benign lesions showed diffuse and essentially uniform membrane staining of CD44s in nevomelanocytic cells, regardless of lesion size, depth, or extent of dermal involvement. In contrast, semiquantitative analysis (0 to 3+) of the primary melanomas showed heterogeneous and decreased staining of CD44s, which inversely correlated with lesion size (-0.569) and depth of invasion (-0.622 and -0.617 for Breslow's depth and Clark's level, respectively). These results were significant at P < .05. CD44s expression in metastases paralleled that of their respective primaries. None of the benign nevomelanocytic lesions showed CD44v6 staining. In contrast, all of the malignant nevomelanocytic lesions showed cytoplasmic staining of the tumor cells. Pretreatment with chondroitinase did not alter CD44s staining. CD44s expression by immunohistochemical determination is uniform in benign nevomelanocytic lesions. Malignant melanomas show decreased, heterogeneous staining that inversely correlates with increasing size, depth, and level of invasion. CD44 expression may be a prognostic indicator in malignant melanomas. Tumor staining with anti-chondroitin sulfate monoclonal antibodies suggests that CD44s may be expressed as a chondroitin sulfate proteoglycan in primary melanomas.
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PMID:CD44 expression in benign and malignant nevomelanocytic lesions. 895

Cell adhesion molecules mediate cell-cell and cell-matrix interactions, and they are thought to play an important role in tumor invasion and metastasis. Altered expression of integrins and CD44 in renal cell carcinoma has been recently demonstrated, but an association with invasive or metastatic behavior has not been reported. We examined very late activation (VLA) integrin and CD44 expression in 37 renal cell carcinomas and correlated adhesion molecule expression with multiple histological and clinical parameters. Most tumors exhibited positive staining for VLA3 (81%). Approximately one third of the tumors stained positively for VLA6 and CD44, and fewer (27%) were positive for VLA2. Only a few tumors were positive for VLA4 (8%) and VLA5 (14%). Most of the tumors exhibiting positive staining showed a combination of membranous and cytoplasmic staining patterns. Low-grade tumors positive for VLA6 showed a tendency for basilar staining of the tumor cells, whereas high-grade tumors exhibited diffuse cytoplasmic staining. All tumors exhibiting weak or strong positive staining for VLA4 or VLA5 showed extrarenal invasion or were known to have developed metastases at the time of nephrectomy. All tumors strongly positive for VLA2 or CD44 showed invasion beyond the renal capsule or metastases. In contrast to a previous study, no association was observed between positive staining and tumor grade. Nor were tumor size, architectural pattern, cell type, or DNA ploidy found to be associated with particular staining patterns. Although many of the invasive tumors showed no difference in VLA integrin or CD44 expression compared with tumors confined to the kidney, increased expression in some of them suggests that these cell adhesion molecules may contribute to the invasive or metastatic phenotype.
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PMID:Correlation of very late activation integrin and CD44 expression with extrarenal invasion and metastasis of renal cell carcinomas. 895 11

Alternative splicing gives rise to numerous CD44 isoforms, some of which seem to have a role in tumour metastasis. Specifically, a variant form of CD44 with sequences encoded by exon v6 (CD44v6) confers metastatic potential when transfected into a nonmetastasizing cell line of rat pancreatic adenocarcinoma. This study has investigated standard CD44 (CD44s) and CD44v6 expression immunohistochemically in 6 samples of normal pancreatic tissue, 4 of tissue affected by chronic pancreatitis, and 24 of tissue from metastasizing and nonmetastasizing pancreatic adenocarcinomas. In addition, 18 samples from lymph node or visceral metastases were included in the study. CD44s was expressed in nonneoplastic tissue and in tissue from pancreatic adenocarcinomas. In contrast, CD44v6 was not detected in any of the normal tissue or chronic pancreatitis specimens, whereas 54% of pancreatic adenocarcinomas and 55% of metastases expressed this variant exon. Although it is not clear whether CD44 isoforms containing exon v6 play a part in malignant progression in the human exocrine pancreas, it seems plausible that the expression of multiple isoforms containing this and other variant exon confers a selective advantage on pancreatic adenocarcinoma.
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PMID:Differential expression of CD44v6 in adenocarcinoma of the pancreas: an immunohistochemical study. 897 53

Hepatoblastoma is an embryonal tumour of the liver, which often contains tissue components with multidirectional differentiation. The occurrence of cell surface antigens in this tumour has not been studied systematically, and we therefore investigated 20 hepatoblastomas for the expression of common acute lymphoblastic leukaemia antigen (CALLA) and cell adhesion molecules (CAMs) in their different tissue components. Epithelial tumour cells of fetal differentiation contained E-cadherin. This protein did not occur in tumour areas with embryonal or mesenchymal differentiation. In contrast, immature embryonal and anaplastic cells expressed CALLA and the hyaluronate receptor (HCAM, CD44). Both fetal and embryonal areas stained irregularly positive for ICAM-1, which, in contrast, was not present on anaplastic cells. Immature fibrous tissue did not contain any of these molecules except for ICAM-1. However, some cells adjacent to, or enclosed in, osteoid were positive for HCAM and NCAM. Like small undifferentiated hepatoblastoma cells, primitive mesenchymal spindle-shaped cells also expressed CALLA, HCAM, and the polysialylated embryonic form of NCAM strongly. This last is not present on other epithelial or mesenchymal tumour cells. Hepatoblastoma cells of varying differentiation express distinct patterns of CAMs and CALLA. Our results give further insight into their histogenesis and cellular interactions and may explain their variable ability for invasive growth and formation of metastases.
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PMID:Expression of cell adhesion molecules and common acute lymphoblastic leukaemia antigen in hepatoblastoma. 897 59

CD44 is the major human cell surface receptor for hyaluronate and functions in a diverse range of physiological processes. Alternative splicing of a single gene generates a family of splice variants (CD44vl-10) in addition to the standard isoform, CD44H. Expression of CD44, particularly CD44v6, has been described to correlate with metastasis formation in various tumours, although evidence in malignant melanoma is inconclusive. In this study, we explored the immunohistochemical pattern of CD44 expression in a range of melanocytic lesions using a panel of monoclonal antibodies raised to CD44H and the variants v3, v4/5, v6 and v8/9. Skin biopsies of 106 lesions from 100 patients were assessed and included benign and dysplastic naevi, melanoma in situ, malignant melanomas in horizontal and vertical growth phase, and cutaneous and lymph node metastases. CD44H was highly expressed in benign and dysplastic naevi and in melanoma in situ. However, expression with melanomas diminished with increasing invasiveness, and the pattern of expression observed correlated significantly with the growth phase of the lesion rather than its Breslow thickness. CD44 splice variants were not detected in any lesions. These results suggest a possible role for downregulation of CD44H in modulating the biological behaviour of malignant melanoma.
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PMID:CD44 expression in melanocytic lesions: a marker of malignant progression? 897 6

The membrane glycoprotein CD44 may be associated with aggressive behavior, dissemination, and poor prognosis of a variety of human tumors. In order to extend our knowledge on the expression and significance of CD44 in cells of the dispersed neuroendocrine system we investigated a spectrum of 134 neuroendocrine tumors, including pituitary adenomas, medullary thyroid carcinomas, parathyroid adenomas, pheochromocytomas, neuroblastomas, small-cell lung carcinomas, and bronchopulmonary, pancreatic, and gastrointestinal neuroendocrine tumors immunohistochemically for CD44 standard and variant exon-encoded gene products (CD44v3, -v4, -v5, -v6, -v9). Furthermore, we compared protein expression with that of CD44 mRNA by reverse-transcriptase PCR and Southern blot hybridization in a subset of tumors. Our results show that CD44 expression is correlated with the "histogenetic origin" of the appropriate neuroendocrine neoplasm. Endoderm-derived tumors generally express 3'-end CD44 variant exon-containing isoforms, whereas neural crest-derived tumors rarely are positive for CD44. Furthermore, we provide evidence that CD44 expression is not correlated with metastatic disease or a particular hormonal phenotype but exhibits an association with the degree of cellular differentiation. Thus, CD44 is not useful as marker for malignancy or prognosis. The number of patients with clinical follow-up data in our study was too small to allow definite conclusions about a possible correlation between CD44 expression and prognosis. But CD44 may help to better classify neoplasms with an unclear neuroendocrine phenotype.
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PMID:CD44 isoform expression in the diffuse neuroendocrine system. II. Benign and malignant tumors. 898 43

Angiogenic and poorly angiogenic tumor variants were obtained by an intraperitoneal inoculation of cells from clones of polyoma-virus transformed BALB/c 3T3 cells into syngeneic mice. The angiogenic tumor cells expressed a higher tumorigenicity phenotype and a higher capacity to produce artificial pulmonary metastases than cells from the poorly angiogenic tumors. The former cells expressed also significantly higher levels of the lymphocyte activation protein Ly-6E.1 than the former cells. The two types of cells did not differ in expression levels of CD44 and of a polyoma-virus specific membrane antigen. These results raise the possibility that the angiogenic phenotype is coregulated with Ly-6. The effect on Ly-6 expression of signal transduction through TNF receptors, functioning as pivotal regulators of angiogenesis was therefore studied. It was found that TNFalpha and more so antibodies against Fas down-regulate expression levels of Ly-6. This down-regulation seemed to be selective as expression levels of CD44 were not affected by this treatment.
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PMID:TNFalpha and anti-Fas antibodies regulate Ly-6E.1 expression by tumor cells: a possible link between angiogenesis and Ly-6E.1. 905 80

Tumor invasion and metastasis are believed to involve the adhesive interaction of tumor cells with extracellular matrix (ECM). This study reports the expression of laminin, fibronectin, thrombospondin, tenascin, and CD44 in rhabdomyosarcoma cells taken from tumors derived from 12 pediatric patients. Twelve paraffin-embedded rhabdomyosarcomas consisting of five alveolar, six embryonal, and one botryoid subtype were examined. All tumors demonstrated positive staining for tenascin and thrombospondin, 10 were positive for fibronectin, 5 positive for laminin, and 4 positive for CD44. Both specimens without cellular staining for fibronectin were of embryonal subtype and no alveolar rhabdomyosarcomas were positive for CD44. No association of the expression of the studied ECM proteins and receptor with the presence of metastatic disease at clinical presentation or with the level of tumor differentiation was found.
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PMID:Cellular expression of adhesion factors in childhood rhabdomyosarcoma. 908 32

Tumor metastasis is one of the most life-threatening aspects of tumor progression in patients with cancer. One of the cell surface molecules that has been implicated to play an important role in tumor metastasis is CD44. Earlier results provide the initial optimism that CD44 isoform expression may be a marker for human cancers. However, more recent studies revealed that regulation of CD44 isoform expression is a complex and not well-understood phenomenon. Expression of CD44 in tumor cells can be regulated quantitatively by increasing the expression of one particular CD44 isoform or quantitatively by altering the expression of CD44 isoforms. Downregulation of CD44 is important in the metastasis of some tumor cells. We summarize some of the recent results on the potential of CD44 as a diagnostic or prognostic marker for patients with cancers.
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PMID:CD44 as a marker in human cancers. 909 May 2

Ovarian cancer cells frequently metastasize by implanting onto the peritoneal mesothelial lining of the abdominal cavity. Data obtained from in vitro adhesion studies have suggested a possible role for the CD44 molecule in this process. The purpose of the present study was to determine the in vivo role of CD44 in ovarian cancer metastasis by using a nude mouse xenograft model of peritoneal implantation. Three groups of 10 athymic female nude mice each received an i.p. inoculum of 10 x 10(6) cells from a CD44-positive human ovarian cancer cell line (36M2) in the presence of either anti-D144 antibody (Ab; nonreactive IgG1), anti-DF3 Ab (reactive IgG1 Ab that does not inhibit in vitro binding), or neutralizing anti-CD44 Ab (IgG1). The number of peritoneal and diaphragmatic implants at 5 weeks for anti-D144 and anti-DF3-treated groups was 103 +/- 17 and 120 +/- 20, respectively (mean +/- SE; P > 0.2). In contrast, animals treated with anti-CD44 Ab experienced a significant reduction in the number of tumor implants (35 +/- 4; P < 0.002). Anti-CD44 Ab was not inhibitory to the growth of 36M2 cells in vitro and did not inhibit s.c. tumor growth in vivo, suggesting that the observed effect was related to inhibition of peritoneal implantation. These data suggest that the CD44 molecule plays an important in vivo role in ovarian cancer cell implantation and that strategies to inhibit CD44 function may represent a novel approach to limiting the intra-abdominal spread of this highly lethal tumor.
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PMID:In vivo inhibition of CD44 limits intra-abdominal spread of a human ovarian cancer xenograft in nude mice: a novel role for CD44 in the process of peritoneal implantation. 910 3


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