NG2 is a 500 KDa membrane chondroitin sulfate proteoglycan expressed on the surfaces of numerous cell-types in the developing embryo, and is found to be also expressed in several types of cancerous cells which include chondrosarcomas, gliomas, and melanomas. While the widespread expression of NG2 on melanomas suggest its importance in melanoma progression, the exact role NG2 may play ha not been determined. The overall goal of this research proposal is to ascertain the role the NG2 proteoglycan may play in the development, growth, progression, and metastasis of melanomas. Our goal will be to identify extracellular ligands which may be important for tumor development and progression. These interactions will then be characterized utilizing biochemical and molecular techniques. Particular emphasis will be placed upon characterizing the interaction between NG2 and two putative ligand, CD44 and the a4B1 integrin. In vitro studies will be undertaken to determine how nG2 expression affects the growth, adhesion, motility, and invasiveness of melanoma cells in culture. NG2+ and NG2- variants of several different cell lines will be injected into mice and the effect of nG2 expression on growth and metastasis of melanomas will be examined.
Goretzki, L; Burg, M A; Grako, K A et al. (1999) High-affinity binding of basic fibroblast growth factor and platelet-derived growth factor-AA to the core protein of the NG2 proteoglycan. J Biol Chem 274:16831-7 |
Burg, M A; Grako, K A; Stallcup, W B (1998) Expression of the NG2 proteoglycan enhances the growth and metastatic properties of melanoma cells. J Cell Physiol 177:299-312 |
Burg, M A; Nishiyama, A; Stallcup, W B (1997) A central segment of the NG2 proteoglycan is critical for the ability of glioma cells to bind and migrate toward type VI collagen. Exp Cell Res 235:254-64 |