Melanoma Cell Invasive and Metastatic Potential Correlates with Endothelial Cell Reorganization and Tenascin...

A direct correlation was observed between the invasive and metastatic potential of A375 melanoma cells and their expression of tenascin and ability to support endothelial cell adhesion and reorganization. Since the ability to metastasize and establish a neovasculature requires interaction of tumor cells with extracellular matrix and endothelial cells, we examined the potential of matrix proteins synthesized by three melanoma cell lines with low-A375P, medium-A375M and high-A375SM invasive and metastatic properties to induce adhesion and rearrangement of human umbilical vein endothelial cells (HUVECs) in vitro. HUVECs adhered to and reorganized into a network of connecting and aligned cells on wells conditioned by A375SM and A375M but not A375P cells. These changes in morphology suggested differences in matrix composition among the three melanoma cell lines. In comparison to low levels of substrate-bound fibronectin and laminin, increasingly higher levels of substrate-bound tenascin were synthesized by the A375P, A375M, A375SM cell lines. HUVEC adhesion and reorganization on A375-conditioned matrix was tenascin-dependent and could be inhibited with antibodies against human tenascin. HUVEC adhesion to A375SM-conditioned matrix and tenascin require α(v)β(3) while reorganization may require α2β1 as well. Our results suggest that tenascin plays a role in integrin-dependent adhesion and reorganization of HUVECs in response to the extracellular matrix of metastatic melanoma cells.