Cell substratum interactions play an important role in adhesion, migration, growth, and differentiation of cells. These interactions are frequently altered in malignant cells. This proposal focuses on the molecular characterization of the cell-matrix interactions and their participation in physiologic and pathologic phenomena. We have found that the cell attachment site in fibronectin, vitronectin, fibrinogen, and apparently also in von Willebrand factor is an arginine-glycine-aspartic acid tripeptide. We have also isolated cell surface receptors which specifically recognize Arg-Gly-Asp sequences in these proteins. Continuing studies on the Arg-Gly-Asp recognition system will aim at a complete molecular description of the receptor-Arg-Gly-Asp interactions and the elucidation of the role of these and other related cell surface recognition systems in cell adhesion, growth and differentiation in vitro, and cell migration, tissue localization and tumorigenicity in vivo. The structure and biological roles of proteoglycans is being examined using molecular cloning of their core proteins. Proteoglycan core protein cDNAs already cloned or to be cloned will be used to derive sequence information on the core proteins. The cDNAs and the corresponding genes will also be used to express proteoglycans or to suppress the existing expression of proteoglycans in tissues and cultured cells. Results of this work will allow determination of the effects of proteoglycan expression on cellular properties such as cell adhesion and invasiveness of tumor cells.
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