RETINOIC ACID-INDUCED INHIBITION OF METASTATIC MELANOMA CELL LUNG COLONIZATION AND ADHESION TO ENDOTHELIUM AND SUBENDOTHELIAL EXTRACELLULAR-MATRIX

The effect of pretreatment of metastatic B16 melanoma cells with 10(-6)M all trans-retinoic acid resulted in a significant inhibition of lung colonization following injection of 10(5) cells into the tail vein of syngeneic C57BL mice. Adhesion of melanoma cells to vascular endothelial cell monolayers, and subendothelial extracellular matrix was also inhibited by pretreatment with retinoic acid, as was tumor cell aggregation following seeding of pretreated cells on to 0.5% agar. Release of (SO4)-S-35 from radiolabelled subendotheliaL extracellular matrix by melanoma cells was essentially unaltered by retinoic acid pretreatment, as was the release of radiolabel from [H-3]proline-labelled matrix, while plasminogen activator activity was enhanced in retinoic-acid-treated cells. These observed changes in adhesive properties may be responsible, at least in part, for the retinoic-acid-induced inhIbition of lung colonization.