Alpha-melanocyte-stimulating hormone blocks invasion of reconstituted basement membrane (Matrigel) by murine B16 melanoma cells.
We have examined the effect of alpha-melanocyte-stimulating hormone (alpha-MSH) on invasive ability of murine melanoma cell lines with different metastatic potential in a Matrigel invasion assay. alpha-MSH potently blocked the invasion of B16-BL6 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 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 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. alpha-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 alpha-MSH. The 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 metastatic properties of B16 melanoma cells, and the degree of inhibition was associated with metastatic potential of B16 melanoma cells.
Murata
J
J
Department of Pathogenic Biochemistry, Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, Japan.
Ayukawa
K
K
Ogasawara
M
M
Fujii
H
H
Saiki
I
I
D000818:Animals; D001672:Biocompatible Materials; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen; D000242:Cyclic AMP / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D018093:Gelatinases / Q000096:biosynthesis / Q000187:drug effects; D007797:Laminin; D008175:Lung Neoplasms / Q000556:secondary*; D008546:Melanoma, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D011509:Proteoglycans; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000521:alpha-MSH / Q000494:pharmacology*
D001672:Biocompatible Materials; D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; C059485:matrigel; D000521:alpha-MSH; D003094:Collagen; D000242:Cyclic AMP; D018093:Gelatinases