Paracrine growth response as a major determinant in liver-specific colonization by in vivo selected B16 murine melanoma cells.

We investigated the respective roles of specific adhesion and paracrine growth stimulation in preferential liver colonization by an in vivo selected B16 murine melanoma cell line (B16-LS9). Comparison of B16-LS9 cells with a lung-specific B16 melanoma cell line (B16-F10) revealed no significant differences between their adhesion properties in vitro, or their immediate organ retention pattern in vivo after tail vein injection. In contrast, B16-LS9 cells grew at slower rates in vitro than B16-F10, unless hepatocytes in coculture, or a liver plasma membrane-extract, were present. In vivo, tumors produced by B16-LS9 cells after subcutaneous or intrafootpad injection also grew at slower rates than those produced by B16-F10, and appeared to progressively lose their liver specificity. However, after intravenous (tail vein) or intrasplenic inoculation, liver colonization was much more pronounced with B16-LS9 than B16-F10 cells. These data indicate that liver colonization by the B16-LS9 cell line depends primarily on the inability of these cells to grow efficiently at sites other than the liver. The liver can indeed provide these cells with a growth-stimulating factor which we found associated with its plasma membrane fraction (i.e. juxtacrine growth stimulation).