EXPRESSION OF THE NG2 PROTEOGLYCAN ENHANCES THE GROWTH AND METASTATICPROPERTIES OF MELANOMA-CELLS

The human homologue of NG2, the human melanoma proteoglycan (HMP), is expressed on most human melanomas. To investigate the role of th is pr oteoglycan in melanoma progression, we have attempted to identify func tionally important molecular ligands for NG2. Immunohistochemical anal ysis of cell lines that endogenously express NG2/HMP suggests that NG2 /HMP associates with CD44 and alpha(4)beta(1) integrin, two molecules previously implicated in melanoma progression. Transfection of rat NG2 into the NG2-negative B16 mouse melanoma cell line also resulted in a highly colocalized pattern of expression between the transfected rat NG2 and the endogenously expressed mouse CD44 and alpha(4)beta(1) inte grin molecules. In functional assays, expression of NG2 decreased the adhesion of B16 melanoma cells to CD44 monoclonal antibodies, hyaluron ic acid, the C-terminal 40-kDa fibronectin fragment, and the CS1 fibro nectin peptide, suggesting that NG2 may negatively modulate CD44- and alpha(4)beta(1)-mediated binding events. Expression of NG2 increased t he proliferation of melanoma cells in culture and increased tumorigeni city in vivo. Moreover, NG2 expression led to increased lung metastasi s of B16F1 and B16F10 melanoma cells in experimental metastasis studie s. Together, these studies demonstrate that NG2 is capable of modulati ng the adhesion, proliferation, and metastatic potential of melanoma c ells, J. Cell. Physiol. 177:299 -312, 1998. (C) 1998 Wiley-Liss, Inc.