α-melanocyte-stimulating hormone blocks invasion of reconstituted basement membrane (Matrigel) by murine B16 melanoma cells

We have examined the effect of α-melanocyte-stimulating hormone (α-MSH) on invasive ability of murine melanoma cell lines with different metastatic potential in a Matrigel invasion assay. α-MSH potently blocked the invasion of B16-BLG cells with highly metastatic potential in a concentration-dependent manner, whereas it was less effective in inhibiting the invasion of weakly metastatic B16-F1 cells. Pretreatment of B16-BL6 cells with α-MSH resulted in a decrease of the adhesiveness to fibronectin and laminin substrates in a time-dependent fashion. As assessed by zymographic analysis, α-MSH partially inhibited 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. α-MSH was more potent in inhibiting the migration 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 α-MSH. The number of lung tumor colonies markedly decreased when B16-BL6 cells were coinjected intravenously with 10^-6 M α-MSH. However, α-MSH had no effect on the experimental lung metastases by B16-F1 cells. These results suggest that α-MSH suppressed the invasive and metastatic properties of B16 melanoma cells, and the degree of inhibition was associated with metastatic potential of B16 melanoma cells.