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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is known from a variety of experimental systems that the ability of tumor cells to grow locally and metastasize can be affected by the presence of adjacent normal tissues and cells, particularly mesenchymally derived stromal cells such as fibroblasts. However, the comparative influence of such normal cell-tumor cell interactions on tumor behavior has not been thoroughly investigated from the perspective of different stages of tumor progression. To address this question we assessed the influence of normal dermal fibroblasts on the growth of human melanoma cells obtained from different stages of tumor progression. We found that the in vitro growth of most (4 out of 5) melanoma cell lines derived from early-stage radial growth phase or vertical growth phase metastatically incompetent primary lesions is repressed by coculture with normal dermal fibroblasts, suggesting that negative homeostatic growth controls are still operative on melanoma cells from early stages of disease. On the other hand, 9 out of 11 melanoma cell lines derived from advanced metastatically competent vertical growth phase primary lesions, or from distant metastases, were found to be consistently stimulated to grow in the presence of dermal fibroblasts. Evidence was obtained to show that this discriminatory fibroblastic influence is mediated by soluble inhibitory and stimulatory growth factor(s). Taken together, these results indicate that fibroblast-derived signals can have antithetical growth effects on metastatic versus metastatically incompetent tumor subpopulations. This resultant conversion in responsiveness to host tissue environmental factors may confer upon small numbers of metastatically competent cells a growth advantage, allowing them to escape local growth constraints both in the primary tumor site and at distant ectopic tissue sites.
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PMID:Fibroblast cell interactions with human melanoma cells affect tumor cell growth as a function of tumor progression. 206 80

As many as 40% of all primary cutaneous melanomas can have histologic remnants of nevomelanocytic nevi adjacent to the tumor. There is increasing evidence that dysplastic nevi are at least a clinical marker for melanoma risk. Spitz nevi are not known for such an association, but are noteworthy because of their histologic appearances. Spitz and dysplastic nevi were studied by flow cytometry to search for DNA abnormality. The study material consisted of formalin-fixed, paraffin embedded material of 41 dysplastic nevi and 14 Spitz nevi. Four cases of dysplastic nevi were excluded for technical reasons. Of the 37 interpretable histograms from dysplastic nevi, 28 (76%) were diploid and nine (24%) were aneuploid. All the Spitz nevi were diploid. Thus, dysplastic nevi, but not Spitz nevi, share aneuploidy features in some cases with melanoma. Previous authors have demonstrated aneuploidy in melanoma with aggressive behavior and in those in deep vertical growth phase. Aneuploidy may be a feature of early as well as late stages of tumor progression regarding the nevomelanocyte system.
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PMID:Evaluation of DNA ploidy in dysplastic and Spitz nevi by flow cytometry. 207 80

Melanoma growth stimulatory activity (MGSA) was originally described as an endogenous growth factor for human melanoma cells. To test the hypothesis that an MGSA autocrine loop is responsible for the partial freedom from growth control observed in nevocytes and melanoma cells, MGSA growth response and MGSA mRNA/protein levels were examined in these cells compared with normal melanocytes. As a single agent, or in combination with other factors, MGSA stimulated the growth of normal human epidermal melanocytes as well as other growth promoters for melanocytes. Nevocytes were not as responsive to exogenous MGSA as melanocytes. MGSA mRNA was minimal or not detected in cultured normal melanocytes, although the protein was present when the cells were cultured in the presence of serum/growth factors and absent when serum/growth factors were omitted. In contrast, MGSA mRNA was constitutively expressed in the absence of exogenous growth factors in cultures established from benign intradermal and dysplastic nevi and melanoma lesions in different stages of tumor progression. Nevus cultures contained immunoreactive MGSA protein in the presence of serum but were negative or only faintly positive in the absence of serum. Melanoma cell lines were positive for MGSA protein in both the presence and the absence of serum. Thus, continued expression of both MGSA mRNA and MGSA protein in the absence of exogenous hormones or serum factors may correlate with partial freedom from growth control exhibited by malignant melanocytes.
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PMID:Characterization of the role of melanoma growth stimulatory activity (MGSA) in the growth of normal melanocytes, nevocytes, and malignant melanocytes. 209 66

Since tumor progression is dependent on the ability of malignant cells to interact with the extracellular matrix, molecules on the cell surface which mediate cell-substratum interactions are likely to be important regulators of tumor invasion and metastasis. The purpose of this study was to examine the distribution of one such group of cell adhesion receptors, the integrins, in benign and malignant lesions of human melanocytes. The distribution of integrin adhesion receptors was defined on cells in culture derived from normal and malignant melanocytes and in tissue sections from benign to increasingly malignant melanocytic lesions using a panel of monoclonal antibodies against specific integrin subunits. Cells in culture expressed a large variety of integrins, including all of the previously characterized members of the beta 1 subfamily plus the alpha v/beta 3 vitronectin receptor. The expression of integrins was similar in cells cultured from either benign or malignant lesions. In contrast, consistent differences were noted in integrin expression by cells within tissues containing metastatic and vertical growth phase melanomas when compared to radial growth phase melanoma cells and cells within nevi. Most notably, the expression of the beta 3 subunit was restricted exclusively to cells within vertical growth phase and metastatic melanomas. The presence of this integrin may be important in the development of tumor invasiveness and could be useful as a marker of melanoma cells entering the more aggressive phase of the malignant process.
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PMID:Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. 220 39

The formation and propagation of several subpopulations of human melanoma cells from a heterogeneous parental population was accomplished with the use of the Membrane Invasion Culture System (MICS) in vitro under sterile conditions. Five sequentially selected subpopulations of melanoma cells showed an increasing ability to do the following: a) invade reconstituted basement membranes in vitro; b) form experimental lung metastases in vivo; and c) express steady-state levels of human type IV collagenase, a marker for metastatic potential. In addition, the morphology and expression of 35S-methionine-labeled cell surface proteins changed with sequential selection. The adaptation of the MICS assay for studying tumor cell subpopulations allows the morphological, biochemical and molecular characterization of events associated with tumor progression in an in vitro model.
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PMID:Selection of invasive and metastatic subpopulations from a heterogeneous human melanoma cell line. 222 75

To determine the extent of nuclear DNA abnormalities and their relationship with prognosis of stage II malignant melanoma, metastatic melanomas in lymphadenectomy specimens of 22 patients were studied by a computerized digital imaging system. The DNA ploidy pattern was aneuploid in 86% of the cases and tetraploid in the remaining 14%. In metastatic melanomas, there was a single clone in one third of patients and multiple clones in the remaining two thirds. Poor survival rate was associated with multiple clones and greater than 30% of mean coefficient of variation of DNA content. With tumor progression stem-cell lines often became heterogeneous with the development of multiple clones and widespread DNA values. These abnormalities, determined by nuclear DNA ploidy analysis, provide useful prognostic information.
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PMID:Nuclear DNA measurements of metastatic melanoma by a computerized digital imaging system. 222 18

This investigation examined the effect of retinoic acid on tumor progression and immunological status of mice bearing the B16-F10 melanoma (previously selected for high lung-colonizing capacity). Tumor cells were implanted s.c. in syngeneic C57BL/6 mice, half of which were treated with beta-all trans retinoic acid (RA). Although RA failed to exhibit direct toxicity on this variant at the concentration used, the immunologic aberrations induced by the tumors were diminished by i.p. RA administration (at 45 micrograms twice/week for 3 weeks). In mice bearing B16-F10 tumors, tumor burdens were decreased from 2.9% of body weight to 1.6%. The mitogenic responses of splenic lymphocytes to concanavalin A (ConA) were increased in tumor-bearing mice following this RA treatment. The presence of these tumor cells decreased the absolute number of CD4- and CD8-positive splenic lymphocytes. Following RA treatment, the CD8-positive population was increased in tumor-bearing mice, while the CD4+ population was not significantly altered. Since previous studies indicated that plasma membrane fragments (or vesicles) could alter lymphocyte distributions and proliferative capacities, the in vitro shedding of membrane fragments from B16-F10 tumor cells was assayed and observed to be decreased after continuous treatment of cultures with 10(-6) M RA for 21 days. Membrane shedding from B16-F10 cells was inhibited by 48.5% following RA treatment. Based on these in vivo and in vitro results, we suggest that RA treatment may diminish tumor growth by decreasing tumor-induced immunosuppressive events.
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PMID:Effect of retinoic acid on tumor-mediated immunologic alterations in mice bearing a variant of the B16 melanoma. 224 92

Monolayer cultures of the human melanoma cell lines StML-12, StML-11, StML-14 (third, respectively, twenty-fifth subculture), and SKMel-28 derived from specimens representing different stages of tumor progression were treated with 10-10,000 U/ml rTNF-alpha applied for 72 h. The effects of rTNF-alpha on cell proliferation, DNA synthesis, cell viability, cloning efficiency, cell division, cell morphology, and the immunophenotype were studied in triplicate experiments. The cell line StML-14(3) revealed a significantly dose-dependent reduction of growth due to both cytostatic and cytotoxic activities of rTNF-alpha as well as a decrease of CE. Increased numbers of cells in prophase were observed 24 h after addition of r-TNF-alpha. In addition, dislocation of chromosomes in the metaphase, formation of micronuclei, and dose-dependent increases of cells exhibiting micronuclei and the DNA amount per cell were detected at the end of treatment. On the other hand, only a slight sensitivity to the anti-proliferative effect of rTNF-alpha was observed with StML-14(25) and SKMel-28, whereas StML-12 and StML-11 were significantly resistant. The last four cell lines were serially subcultivated and presented common phenotypic patterns with more malignant characteristics than the cell line StML-14(3) before treatment. Overall, rTNF-alpha enhanced the malignant immunophenotype of the cell lines tested. It increased the expression of the "late" melanoma progression markers A.10.33 and A.1.43, and Ki67, and it decreased the expression of the "early" progression marker K.1.2. The expression of HLA-I, HLA-DR, and ICAM-1 was also enhanced after rTNF-alpha treatment, whereas in contrast to other cytokines, rTNF-alpha did not induce the de novo expression of HLA-DR in HLA-DR-negative melanoma cell lines. These findings indicate that rTNF-alpha induces cytostasis and decreases cell viability of certain rTNF-alpha-sensitive melanoma cells. These effects may result in selection of rTNF-alpha-non-sensitive human melanoma cell populations with higher proliferation rates and a more aggressive immunophenotype in vitro.
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PMID:Cytostatic and cytotoxic effects of recombinant tumor necrosis factor-alpha on sensitive human melanoma cells in vitro may result in selection of cells with enhanced markers of malignancy. 225 39

Drug resistance, which so often accompanies tumor progression, has been shown to be related to changes in membrane properties which may result in decreased drug accumulation in the tumor cell. A correlation between sensitivity to thermochemotherapy and degree of malignancy was found in the AKR lymphoma system. Hyperthermia increased adriamycin (ADR) uptake and concomitantly its cytotoxicity to AKR lymphoma cells. Moreover, these effects were more pronounced on a variant of high malignancy (HM) than on a low malignancy (LM) one. Fluorescent microscopy, as well as cytofluorometry, indicated that lymphoma cells treated by ADR at 43 degrees C were more permeable to the cytotoxic agent than those exposed to the chemotherapeutic substance at 37 degrees C. Cytofluorometry indicated the presence of a minor cell subpopulation with low ADR uptake in the HM variant, not found in the LM one. Fluorocytometry also showed that the temperature-dependent increased ADR uptake was more marked in the HM than in the LM variant, explaining the differential effect of thermochemotherapy on the two lymphoma variants. However, correlation between degree of malignancy and sensitivity to thermochemotherapy is not a general feature. In contrast to the results obtained in the AKR lymphoma system, in the B16 melanoma the low malignancy variant, F1, was more markedly affected by the combined treatment than the F10 variant. The increased cytotoxic effect of ADR by supranormal temperatures in the F1 variant was shown to be due to an augmented drug uptake. The results suggest that drug resistance in late stages of tumor progression can be overcome by an agent acting on the cell membrane. However, the data also indicate the necessity of assaying cancer treatment modalities, including those designed to circumvent drug resistance, on various tumor system models.
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PMID:Sensitivity to thermochemotherapy of AKR lymphoma and B16 melanoma variants of malignancy. 229 12

Based on melanoma pathogenesis, phenotypic dynamics in pigment cell tumor progression detected with 11 MoAb have been defined. Anti-melanosomal A4F11 antibody reacts with every type of pigment cell tumor tested except for a few specimens. TNKH1 and anti-K.1.2 antibodies recognize nevocytic benign to premalignant tumors. HLA-DR, A.1.43, and A.10.33 antigens are expressed in advanced melanomas. Staining with anti-ganglioside GM3 and GD3 antibodies, M2590 and 4.2, respectively, reveals that most pigment cell tumors express gangliosides GM3 and GD3. But A2B5 antibody, which detects some polysialogangliosides such as GQ1C, reacts with highly progressed melanoma cells. Anti-ras p21 antibodies, RASK-3 and RASK-4, react with malignant melanomas and their premalignant lesions. These findings suggest the following: A4F11 is a universal marker of pigment cell tumors. TNKH1 and anti-K.1.2 antibodies might not be markers of melanocytic tumors but of nevocytic benign to premalignant tumors. Melanoma cells express gangliosides GM3 and GD3 as common pigment cell antigens and synthesize aberrant polysialogangliosides. Anti-ganglioside MoAb, including A2B5, are possible markers of the level of malignancy in melanoma cells like anti-A.1.43 and anti-A.10.33 antibodies. Enhanced ras p21 expression already appears on premalignant pigment cells.
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PMID:Antigen dynamics in melanocytic and nevocytic melanoma oncogenesis: anti-ganglioside and anti-ras p21 antibodies as markers of tumor progression. 229 92


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