Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effects of interferons (IFNs) on the attachment, collagenase IV activity, chemotactic migration and in vitro invasion of human melanoma (A2058) cells treated for various time periods with human recombinant interferon alpha (hrIFN-alpha) or gamma (hrIFN-gamma). The cells treated with hrIFN alpha for a short time period attached more readily to purified basement membrane components, type IV collagen and laminin, than control cells. The stimulating effect of hrIFN gamma on the attachment was seen, however, when the cells were treated for a longer period of time (3 days) with this drug. The short-term treatment with hrIFN alpha also enhanced the in vitro invasion of cells through a reconstituted basement membrane compared to findings with untreated control cells. Pre-treatment of 3 days or more was, however, needed for hrIFN gamma to promote the invasion of A2058 cells. Both IFNs increased the secretion of basement membrane (type IV) collagen degrading metalloproteinase (collagenase IV) activity from human melanoma cells. Further, chemotaxis, i.e., directed migration of A2058 cells to laminin, was enhanced by both IFNs. In contrast, the attachment, collagenase IV activity, chemotaxis, and in vitro invasion were markedly inhibited when the cells were treated for an extended time period (7 days) with the IFNs. Interferons also inhibited cell proliferation after 4 days of exposure. These results suggest that time of treatment with interferons modulates the invasive capacity of human melanoma cells in vitro, causing initially a transient enhancement of invasion followed by an inhibition of invasive propensity after extended exposure to these drugs, and that different biochemical steps required for successful invasion are regulated in parallel by interferons alpha and gamma.
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PMID:Recombinant interferon alpha and gamma modulate the invasive potential of human melanoma in vitro. 184 57

Membranes from 2 K1735 murine melanoma clones of high invasive capacity show increased amounts of pertussis toxin (PT) substrate when compared to a weakly invasive cellular counterpart. Using a panel of specific G-protein antibodies, we identified Gi alpha 2 as the PT-sensitive G-protein uniquely abundant in highly invasive cells. In addition, RNA hybridization results confirm the immunoblot observations that Gi alpha 2 is present at higher levels in strongly invasive cells. This result suggests that the elevated expression of Gi alpha 2 in highly invasive cells is not entirely due to differences in either translational efficiency or protein degradation but is related to altered RNA transcriptional initiation, processing and/or degradation. ADP-ribosylation of Gi alpha-subunits by PT inhibited the fibronectin, laminin and collagen type-IV-stimulated motility of the 2 highly invasive clones, while PT treatment of cells from a poorly invasive clone resulted in little or no reduction of the fibronectin, laminin or collagen type-IV-stimulated lower motility. Furthermore, PT treatment of highly or poorly invasive K1735 clones does not result in any alteration in cellular cAMP accumulation, suggesting that the PT substrate is not linked with the adenylyl cyclase enzyme complex. The data suggest that a PT-sensitive G-protein, probably Gi alpha 2 regulates second messenger pathways that contribute to elevated motility in highly invasive K1735 cells.
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PMID:The role of G-protein in matrix-mediated motility of highly and poorly invasive melanoma cells. 185 Mar 81

The ability of cultured human fibroblasts to reorganize and contract three dimensional collagen I gels is regarded as an in vitro model for the reorganization of connective tissue during wound healing. We investigated whether adhesion receptors of the integrin family are involved. It was found that synthesis and transcription of the alpha 2 beta 1 integrin (but not of alpha 1 beta 1 or alpha 3 beta 1) is selectively upregulated when fibroblasts are seeded into type I collagen gels. Time course experiments revealed that high synthetic levels of alpha 2 beta 1 parallel the gel contraction process and return to "baseline" levels after the contraction has subsided. Furthermore, function-blocking mAbs directed to the alpha 2 and beta 1 chain of integrins inhibited gel contraction. Remodelling of connective tissue can be important for tumor cells during invasion and formation of metastases. Therefore, we tested human melanoma cell lines for this function. Five out of nine melanoma lines contracted collagen gels in vitro. Among these, two highly aggressive melanoma cell lines (MV3 and BLM) most efficiently contracted gels almost reaching the rate of normal adult fibroblasts. In these cells, synthesis of alpha 2 beta 1 was also significantly upregulated when seeded into collagen I gels. Moreover, function blocking anti-alpha 2 in conjunction with anti-beta 1 chain mAbs completely inhibited gel contraction for several days. Other melanoma cells (530) with lower metastatic potential which were not able to contract gels, showed no induction of alpha 2 beta 1 synthesis in gel culture. Our results suggest an important role of integrin alpha 2 beta 1 in the contraction of collagen I by normal diploid fibroblasts during wound healing and in the reorganization of collagen matrices by highly aggressive human melanoma cells.
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PMID:Integrin alpha 2 beta 1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collagen I fibrils. 195 83

We compared the properties in human melanoma cell line A875 and rat pheochromocytoma cell line PC12 of nerve growth factor receptor (NGFr). We also analyzed NGFr and a truncated NGFR lacking the cytoplasmic domain, which were transiently expressed in COS cells. The full-length NGFR expressed in COS cells bound nerve growth factor (NGF) with positive cooperativity, but A875 NGFr and truncated NGFr in COS cells did not display positive cooperativity. The anti-human NGFr monoclonal antibody NGFR5 was characterized and found not to compete with NGF for binding to NGFr. Fabs were prepared from NGFR5 and 192, an anti-rat NGFR monoclonal antibody that was previously shown not to compete with NGF for binding. Fluorescein-labeled Fabs were used to measure the distribution and lateral diffusion of the NGFr. NGFr expressed on COS and A875 cells are diffusely distributed, but NGFr on the surface of PC12 cells appeared, for some cells, to be patched. In A875 cells, 51% of the NGFr was free to diffuse with diffusion coefficient (D) approximately 7 X 10(-10) cm2/s. In COS cells, 43% diffused with D approximately 5 X 10(-10) cm2/s. There was no significant difference in diffusibility between the full-length NGFr and the truncated NGFr. We compared NGFr diffusion on PC12 cells in suspension or adherent to collagen-coated coverslips. For suspension cells, we obtained 32% recovery with D approximately 2.5 X 10(-9) cm2/s. On adherent cells, we obtained 17% recovery with 6 X 10(-9) cm2/s. Binding of NGF enhanced lateral diffusion of NGFr in A875 cells and in PC12 cells in suspension but did not alter lateral diffusion of NGFr in COS cells or in adherent PC12 cells. NGF had no effect on the diffusing fraction or the distribution of NGFR for any cell line.
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PMID:Lateral diffusion of nerve growth factor receptor: modulation by ligand-binding and cell-associated factors. 196 90

In order to study the interaction between melanoma cells and collagen, B16 murine melanoma cells were embedded and cultured in type I collagen gel. Melanoma cells cultured in the collagen gel became elongated, as compared with those cultured on plastic, and some of them assumed a dendritic form. The gel contracted very slowly but steadily during culturing of melanoma cells, as in the experiment using fibroblasts. On the 20th day of culture the area of the gel accounted for only 32% of that when culture started. This contraction was enhanced by retinoic acid, which is known to induce cell differentiation. The contractility of the gel differed between various lines of melanoma cells. The present observations raise the possibility of interaction between melanoma cells and type I collagen.
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PMID:Contraction phenomenon of type I collagen gel by melanoma cells. 197 27

The expression of the integrin receptors VLA-1, -2, -3, and -6 was studied in normal cultured melanocytes and in five melanoma cell lines. Normal melanocytes synthesized VLA-3, but did not reveal detectable levels of VLA-1, -2, and -6. All melanoma cell lines, however, expressed VLA-2, -3, and -6. VLA-1 was synthesized by two of five melanoma lines. In parallel, we had analyzed the expression of four previously characterized melanoma cell surface antigens. One of them (antigen A.1.43), which is associated with tumor progression of human melanoma, revealed a striking similarity to VLA-2. In sequential immunoprecipitation experiments, we show that A.1.43 is identical with the integrin VLA-2, a cell surface receptor for collagen, laminin, and fibronectin.
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PMID:Identification of a melanoma progression antigen as integrin VLA-2. 199 90

Expression of alpha and beta subunits of VLA and VNR integrins was analyzed by cytofluorimetric analysis on 6 different human primary and metastatic melanoma cell cultures. Marked inter-tumor heterogeneity was observed, and expression of VLA-alpha I, VLA-alpha 2 and VLA-alpha 6 was lower on primary melanomas than on metastatic lesions. The function of VLA products on melanoma cells was assessed by adhesion assays to extracellular matrix (ECM) proteins using a panel of melanoma clones previously characterized for the presence and heterogeneity of expression of the distinct VLA-alpha subunits. These experiments indicated that intra-tumor heterogeneity in the integrin profile can influence the interaction of neoplastic cells with ECM proteins. Inhibition of adhesion with antibodies to VLA-alpha subunits revealed that the presence on melanoma cells of VLA-alpha 2, VLA-alpha 5 and VLA-alpha 6 is relevant for the adhesion to type-IV collagen, fibronectin and laminin respectively. Culture of tumor cells in the presence of cytokines such as rIL-I beta, rTNF-alpha, rIFN-gamma or TGF-beta I could induce up- or down-modulation in the level of expression of multiple VLA integrins. Cytokine-mediated antigenic shifts in the VLA profile of melanoma cells were detected by cytofluorimetric analysis as early as 24 hr after cytokine exposure. The cytokine-dependent change in the matrix receptor profile of melanoma cells also affected the adhesion to ECM proteins as revealed by the enhanced adhesion of rTNF-alpha-treated cells to fibronectin. These data indicate that constitutive heterogeneity in the integrin profile or cytokine-mediated shifts in VLA expression can affect the ability of human melanoma cells to interact with different ECM components.
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PMID:Heterogeneity for integrin expression and cytokine-mediated VLA modulation can influence the adhesion of human melanoma cells to extracellular matrix proteins. 199 84

A cathepsin-H-like enzyme has been isolated from cultured human melanoma cells (G 361 cell line). The enzyme is similar to cathepsin H(s) of normal tissues in molecular weight, enzymatic characteristics (substrates, inhibitors, pH optima, Km values), and immunoreactivity. The inactive form of the enzyme with a molecular mass of 40 kDa has been found in the culture medium. The inactive enzyme is activated by acid pH, pepsin, and cathepsin-D-like enzyme treatments and converted into a form with a molecular mass of 28 kDa. The activated extracellular cathepsin-H-like enzyme and the active intracellular enzyme exhibit the same characteristics. The melanoma-derived cathepsin-H-like enzyme degrade fibrinogen and fibronectin, but not laminin or type-IV collagen. We conclude that the extracellular cathepsin-H-like enzyme may have important functions, together with other proteinases, in the destruction of extracellular matrix components, thus enabling proliferation, migration, and metastasis to occur.
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PMID:Characterization of a cathepsin-H-like enzyme from a human melanoma cell line. 207 Dec 33

We describe a patient who developed a pigmented plaque on the anterior aspect of his right knee clinically mimicking angiokeratoma circumscriptum or malignant melanoma. Histopathological examination demonstrated a multinodular hemosiderotic dermatofibroma in which the cellular tumor islands were separated by areas of hyalinized collagen. Multinucleated giant tumor cells were found in the lumen of a medium-size vein underlying the tumor. The differential diagnosis of angiomatoid malignant fibrous histiocytoma, a tumor with clinical and morphologic similarities, is discussed.
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PMID:Multinodular hemosiderotic dermatofibroma. 207 65

Novel or modified serum-free media were developed for the anchorage-dependent growth of nontransformed murine mammary epithelial cells (MMEC) and Balb/MK murine keratinocytes respectively. Growth rates for both cell lines were similar in serum-containing and serum-free media. The serum-free media were used to evaluate potential mechanisms of epithelial cell growth regulation by type 1 transforming growth factor beta (TGF-beta 1). The growth of MMEC and Balb/MK cells was reversibly inhibited 40-65% in a time- and dose-dependent fashion by TGF-beta 1 under both serum-containing and serum-free conditions. Constitutive over-expression of a transfected c-myc oncogene in MMEC did not result in loss of sensitivity to growth inhibition by TGF-beta 1. In addition, Balb/MK and MMEC growth inhibition by TGF-beta 1 was not potentiated by polyunsaturated fatty acids or reversed by vitamin E. Exogenous type V collagen was able to mimic the inhibitory effects of TGF-beta 1 on the serum-free growth of Balb/MK and MMEC. In contrast, collagen types I and IV, fibronectin and laminin did not inhibit the growth of these cells. The type V collagen used was not contaminated with TGF-beta, and subsaturating, but not saturating concentrations of type V collagen and TGF-beta 1 were additive with respect to Balb/MK and MMEC growth inhibition. These results demonstrate that nontransformed epithelial cell growth inhibition by TGF-beta 1 is mediated by mechanisms distinct from those observed with certain carcinoma and melanoma cells. Our results also suggest the possible involvement of type V collagen in Balb/MK and MMEC growth inhibition by TGF-beta 1.
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PMID:Evaluation of the role of extracellular matrix proteins, polyunsaturated fatty acids and c-myc expression in the inhibition of the serum-free growth of epithelial cells by TGF-beta 1. 207 65


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