Melanoma chondroitin sulfate proteoglycan regulates matrix metalloproteinase-dependent human melanoma invasion into type I collagen

Tumor cell adhesion and proteolysis of the extracellular matrix proteins su rrounding the cells are tightly linked processes in tumor invasion. In this study, we sought to identify components of the cell surface of a vertical growth phase melanoma cell line, WM1341D, that mediate invasive cellular be havior. We determined by antisense inhibition that melanoma chondroitin sul fate proteoglycan (MCSP) and membrane-type 3 matrix metalloproteinase (MT3- MMP) expressed on WM1341D are required for invasion of type I collagen and degradation of type I gelatin. MT3-MMP co-immunoprecipitated with MCSP in W M1341D melanoma cells cultured on type I collagen or laminin, The associati on between MT3-MMP and MCSP was largely disrupted by removing chondroitin s ulfate glycosaminoglycan (CS) from the cell surface, suggesting CS could me diate the association between the two cell surface core proteins. Recombina nt MT3-MMP and MT3-MMP from whole cell lysates of WM1341D cells were specif ically eluted from CS-conjugated affinity columns. The results indicate tha t MT3-MMP possesses the potential to promote melanoma invasion and proteoly sis and that the formation of a complex between MT3-MMP and MCSP may be a c rucial step in activating these processes.