EXPRESSION OF CONSTITUTIVELY ACTIVATED HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR-RECEPTOR (C-MET) IN B16 MELANOMA-CELLS SELECTED FOR ENHANCEDLIVER COLONIZATION

The murine melanoma B16-LS9 cell line was obtained after repeated pass ages in vivo through the liver of syngeneic mice, and shows an enhance d ability to colonize the liver after intravenous inoculation when com pared to its parental, unselected counterpart B16-F1. We have previous ly shown that paracrine growth effects mainly account for better growt h of B16-LS9 in the liver than at other sites, and more recently we re ported hepatic transferrin as a factor contributing to efficient growt h in the liver. Here we show that increased expression of constitutive ly activated c-met (the receptor for Hepatocyte Growth Factor/Scatter Factor) consistently occurs during selection of B16 cells through the liver. Constitutive activation of c-met seems to follow its own overex pression and not to depend on an autocrine mechanism. As a consequence , liver-selected B16 melanoma cells have higher tyrosine-kinase activi ty and higher amounts of tyrosine-phosphorylated proteins than parenta l B16-F1 or lung-specific B16-F10 cells. Overexpression of constitutiv ely activated c-met enhances motility and invasiveness of B16-LS9 cell s, presumably favoring their colonization efficiency in vivo. However, whether levels of c-met expression also determine the organ-specifici ty of B16 melanoma cells needs further clarification.