ALPHA-MELANOCYTE-STIMULATING HORMONE BLOCKS INVASION OF RECONSTITUTEDBASEMENT-MEMBRANE (MATRIGEL) BY MURINE B16 MELANOMA-CELLS

We have examined the effect of alpha-melanocyte-stimulating hormone (a lpha-MSH) on invasive ability of murine melanoma cell lines with diffe rent metastatic potential in a Matrigel invasion assay. alpha-MSH pote ntly blocked the invasion of B16-BL6 cells with highly metastatic pote ntial in a concentration-dependent manner, whereas it was less effecti ve in inhibiting the invasion of weakly metastatic B16-F1 cells. Pretr eatment of B16-BL6 cells with alpha-MSH resulted in a decrease of the adhesiveness to fibronectin and laminin substrates in a time-dependent fashion. As assessed by zymographic analysis. alpha-MSH partially inh ibited the production of matrix metalloproteinase (MMP)-2 and -9 from both cell lines to a similar degree without affecting the degradative activity of these MMPs. alpha-MSH was more potent in inhibiting the mi gration of B16-BL6 cells towards both fibronectin- and laminin-coated substrates than that of B16-F1 cells. The growth and morphology of B16 -BL6 cells were not changed after a 7-day incubation with alpha-MSH. T he number of lung tumor colonies markedly decreased when B16-BL6 cells were coinjected intravenously with 10(-6) M alpha-MSH. However, alpha -MSH had no effect on the experimental lung metastases by B16-F1 cells . These results suggest that alpha-MSH suppressed the invasive and met astatic properties of B16 melanoma cells, and the degree of inhibition was associated with metastatic potential of B16 melanoma cells.