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

Melanotropin (MSH) receptor activity in the M2R mouse melanoma cell line is tightly controlled by calcium by an unknown mechanism. The possibility that calcium regulation is mediated by calmodulin or a calmodulin-related calcium binding protein has been addressed in this report by studying the effects of two known calmodulin antagonists, fluphenazine and melittin, on MSH receptor function. Stimulation of adenylate cyclase (AC) in M2R plasma membranes by beta MSH was strongly inhibited by both antagonists. The concentrations of fluphenazine and melittin yielding half-maximal inhibition (IC50) of AC were 16 microM and 2.4 microM, respectively. Both fluphenazine and melittin also inhibit prostaglandin E1-, GTP gamma S, and forskolin-stimulated AC activity, as well as that of unstimulated enzyme, although inhibition is shown to occur at significantly higher concentrations of antagonist. We have shown that the calcium-dependent rate-limiting step in MSH stimulation of adenylate cyclase, that of hormone binding, is strongly inhibited by these antagonists at concentrations identical to, if not lower than, those required for the inhibition of AC activity (fluphenazine-IC50, 14 microM; melittin-IC50, 0.7 microM). The actions of these antagonists, furthermore, appear to be calcium insensitive, as melittin affects the stability of both the high affinity (calcium containing) and low affinity (calcium depleted) receptor-MSH complexes. The sensitivity of the MSH receptor to inhibition by calmodulin antagonists resembles that described for purified calmodulin-sensitive enzyme systems, which suggests a possible role for calmodulin in MSH receptor function. Among peptide hormone receptors, this effect by calmodulin antagonists appears to be unique for the MSH receptor.
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PMID:Inhibition by melittin and fluphenazine of melanotropin receptor function and adenylate cyclase in M2R melanoma cell membranes. 366 46

A B16 mouse melanoma cell line resistant to doxorubicin was obtained by continuous in vitro exposure to the drug. The ID50 for this line was 200 times higher than that for the parental cell line. The resistant cell line had some biological characteristics similar to those of the sensitive parental cell line, like saturation density and protein content. Differences were found in doubling time which was longer, cloning efficiency which was lower and DNA content which was higher in the resistant as compared to the parental line. Intracellular distribution of doxorubicin was also different having a nuclear-cytoplasmic ratio higher in sensitive than in resistant cells. Melanin content was an unstable feature in the sensitive cell line, whereas melanin was always present in resistant cells. Resistance to doxorubicin was maintained during 50 in vitro passages in the absence of the drug. Cross-resistance was found with vincristine and other anthracyclines, like daunorubicin and 4'-epi-doxorubicin but not with cis-platinum, and a new doxorubicin derivative, 4'-deoxy-4'-iodio-doxorubicin. The B16 line showed a lower resistance index to 4'-deoxy-doxorubicin and 4-demethoxy-daunorubicin (30 and 3 respectively), as compared to doxorubicin. Doxorubicin-resistance was partially circumvented by pretreatment of resistant cells with verapamil, a calcium chelating agent, and by trifluoperazine, a calmodulin-antagonist.
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PMID:Characterization of a doxorubicin-resistant murine melanoma line: studies on cross-resistance and its circumvention. 373 Feb 55

We have identified a cDNA whose sequence is preferentially expressed when quiescent fibroblasts are stimulated to proliferate. The steady-state levels of the mRNA corresponding to this clone, called 2A9, are increased by serum, platelet-derived growth factor, and epidermal growth factor, but not by insulin or platelet-poor plasma. mRNA levels of 2A9 are also increased in human acute myeloid leukemia. The 2A9 cDNA has been molecularly cloned from an Okayama-Berg library, and its complete nucleotide sequence has been determined. It has an open reading frame of 270 nucleotides, which has a 55% homology with the coding sequence of the beta-subunit of the S-100 protein, a calcium-binding protein that belongs (like calmodulin and the vitamin D-dependent intestinal calcium-binding protein) to the family of calcium-modulated proteins and is found in abundance in several human tumors, including melanoma. The S-100 protein and the deduced aminoacid sequence of 2A9 are also partially homologous to the small subunit of a protein complex that serves as a cellular substrate to tyrosine kinase. The partial homology of 2A9 (whose RNA is inducible by growth factors and is overexpressed in human acute myeloid leukemias) to the S-100 protein, other calcium-modulated proteins, and the subunit of a substrate for tyrosine kinase, is particularly interesting in view of the role attributed to calcium and tyrosine kinases in the regulation of cell proliferation.
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PMID:Molecular cloning of the cDNA for a growth factor-inducible gene with strong homology to S-100, a calcium-binding protein. 375 24

Using unselected and selected B16 melanoma cell lines, we examined the relationship between homotypic aggregation properties and the potential to form experimental metastatic lung colonies. The B16 sublines were selected in vitro from a line with relatively low homotypic aggregation kinetics and experimental metastatic potential (B16-F1) by successive steps of cell aggregation, followed by separation of cell aggregates from single cells. The selected sublines possessed significantly higher rates of aggregation than did the parental cell line and, when injected intravenously as single cells, formed greater numbers of lung tumor colonies. The aggregation kinetics of the parental and selected cell lines were dependent on divalent cations, with the following order of selectivity: Ca2+ greater than Mn2+ much greater than Mg2+. Syngeneic and xenogeneic serum components and the protease inhibitor leupeptin enhanced the aggregation kinetics of various B16 cell lines. The results support the proposal that a positive correlation exists between increased homotypic adhesion and experimental metastatic potential.
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PMID:Malignant melanoma cell lines selected in vitro for increased homotypic adhesion properties have increased experimental metastatic potential. 379 26

The Ca2+-dependent cell-cell adhesion system (CDS) is thought to be essential for the formation and maintenance of cell adhesion in a wide variety of tissues. Previous studies suggested that CDS has some cell-type specificity; for example, the monoclonal antibody ECCD-1 selectively recognizes CDS of certain epithelial tissues in mouse embryos but not nervous tissues. In the present study, we have obtained a monoclonal antibody, designated NCD-1, that disrupts connections between brain cells of mouse embryos. A series of experiments suggested that NCD-1 specifically recognizes CDS. We then determined the distribution of the NCD-1 antigen in various mouse tissues. NCD-1 reacted with cells of the following tissues and cell lines: nervous tissues from various sources, lens, striated muscle, cardiac muscle, glioma G26-20, adrenocortical tumor Y1, and melanoma B16. None of these cells reacted with ECCD-1, and the cells reactive with ECCD-1 did not react with NCD-1. There was also a class of cells that did not react with either ECCD-1 or NCD-1. These results suggest that cells in the body can be classified into at least three groups containing CDS of differing specificities. A map of the tissue localization of these different classes of CDS also suggests that the expression of cell-type-specific cell adhesion molecules in each tissue plays a crucial role in adhesion between the same cell types and segregation of different cell types in processes essential for animal morphogenesis.
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PMID:A monoclonal antibody disrupting calcium-dependent cell-cell adhesion of brain tissues: possible role of its target antigen in animal pattern formation. 385 14

Verapamil, a calcium antagonist, inhibited both experimental (IV inoculation of tumor cells) and spontaneous metastasis (SC inoculation) of the highly metastatic B16 melanoma and colon adenocarcinoma 26 cell lines. Verapamil treatment resulted in a maximum 80% inhibition of metastases, the degree of inhibition varying among the different metastatic systems. Verapamil inhibited platelet aggregation induced by these tumor cell lines, the patterns of inhibition being different for B16 melanoma and colon adenocarcinoma. The inhibition of platelet aggregation induced by tumor cells is proposed as a mechanism by which the calcium antagonist exerts its antimetastatic effect. These results, together with our previous findings that calcium antagonists can increase the cytotoxicity of drugs in tumor cells with induced or inherent drug resistance by inhibiting outward transport of the drug, indicate that calcium antagonists have potential as a new class of adjuvant agents in the field of cancer chemotherapy.
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PMID:Inhibition of spontaneous and experimental tumor metastasis by the calcium antagonist verapamil. 396 58

Flunarizine, a calcium-antagonist drug that binds to calmodulin, was found to inhibit the migration of both B16 melanoma cells and M5076 macrophage-like cancer cells. The migration movement, both under agarose and through a polycarbonate filter membrane, was impaired by the drug. In M5076 macrophage-like cells Fc-dependent as well as Fc-independent phagocytosis were also found significantly reduced by flunarizine. Results are discussed in relationship with the previously observed effects of the drug on the growth rate of B16 melanoma cells in vitro.
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PMID:Effects of a calcium-antagonist (flunarizine) on cancer cell movement and phagocytosis. 401 40

The aggregating properties of murine melanoma cell lines with low metastatic potential (B16-F1) and high metastatic potential (B16-F10 and B16-BL6) were compared. All three types of cells were found to possess Ca2+-dependent and Ca2+-independent intrinsic mechanisms for cell adhesion, though the extent of reaggregation varied in each mechanism. After trypsin treatment at around 1 microgram/ml, F10 and BL6 cells reaggregated in the presence of 1mM Ca2+ to a greater degree than F1 cells. F10 and BL6 cells were also more aggregative than F1 cells after dissociation with collagenase. The apparent adhesiveness of the cells was found to be dependent on both the manner of cell preparation for reaggregation and on the presence of external Ca2+ or serum factors. The results are discussed in relation to the mechanisms of tumor cell arrest with emphasis on the effect of extracellular factors on cell adhesiveness.
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PMID:Adhesive properties of weakly and highly metastatic melanoma cell lines. 608 47

Calmodulin antagonists inhibited hormone-stimulated cyclic AMP accumulation in both cultured cells and cell lysates of mouse B16 melanoma. Particulate preparations of B16 melanoma contained 34-45% of total cell calmodulin, which could not be dissociated by extensive washing irrespective of the presence of EGTA in the buffer. The adenylate cyclase activity in such preparations was unaffected by the addition of exogenous calmodulin. However, the rare-earth-metal ion La3+, which can mimic or replace Ca2+ in many systems, produced an immediate inhibition of agonist-stimulated adenylate cyclase activity and preincubation of particulate preparations was La3+ followed by washing with La3+-free buffer dissociated calmodulin (96% loss) from particulate preparations. The loss of calmodulin from particulate preparations was associated with a decrease in agonist responsiveness (74%) and a marked change in the Ca2+-sensitivity of the enzyme, low concentrations of calcium (approx. 10 nM) now failing to stimulate enzyme activity, high concentrations of calcium (greater than or equal to 100 nM) producing greater-than-normal inhibition of enzyme activity. Direct activation of adenylate cyclase by the addition of pure calmodulin was now demonstrable in such calmodulin-depleted particulate preparations. Half-maximal stimulation of agonist-responsive adenylate cyclase occurred at 80 nM-calmodulin in the presence of 10 microM free Ca2+. Maximal stimulation by calmodulin (at 300-600 nM) restored enzyme activity to 89 +/- 5% (mean +/- S.E.M., n = 7) of the activity in untreated, calmodulin-intact, preparations.
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PMID:Calmodulin activation of adenylate cyclase in the mouse B16 melanoma. 609 17

Seven strains of normal human cells (fibroblastic, skin epithelioid, and amniotic) ceased to proliferate in medium depleted of free calcium ion by titration with ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), whereas the growth of 9 of 10 human melanoma cell lines was not affected. Fibroblasts showed a rapid drop in thymidine pool size and decreased incorporation of thymidine and uridine when treated with EGTA, followed during the next 48 hr by a decrease in plasma membrane potential and by development of a proliferative block in the G1 phase of the cell cycle. The calcium-independent melanoma line MM96 exhibited an early decrease in thymidine pool size and enhanced incorporation of nucleosides but continued to proliferate with little perturbation of the cell cycle or change in membrane potential. Tumor cell DNA may therefore be selectively labeled in the presence of normal cells. The anomalous, calcium-dependent melanoma line (MM170) showed an immediate increase in the thymidine pool size and in nucleoside incorporation and subsequently accumulated in G1 and G2 with diminution of membrane potential and of DNA and RNA synthesis. The proliferative block in MM170 cells could be reversed by addition of calcium ion or by replacement with control medium. Addition to the medium of all 8 nucleosides (50 microM), singly or together, did not prevent EGTA-induced cytostasis in fibroblasts or MM170; transport of thymidine across the cell membrane was enhanced by 24-hr EGTA treatment in fibroblasts, MM96, and MM170. Thus, although calcium affected thymidine utilization rapidly and differently in each of the three cell types, nucleoside starvation per se did not appear to be responsible for either type of proliferative block.
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PMID:Effects of calcium depletion on human cells in vitro and the anomalous behavior of the human melanoma cell line MM170. 618 41


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