The mechanisms of adhesion of fibroblasts to a model extracellular matrix, serum-coated tissue culture substratum, are being studied as well as the alteration of these mechanisms upon transformation of these cells with oncogenic viruses into tumorigenic derivatives. Detachment of cells from the substratum with the Ca++ specific chelator EGTA and gentle agitation leaves focal adhesive material from the cell surface as substratum-attached material (SAM). SAM is derived from the tight, focal contacts of these cells as well as some close contact material. This adhesive material is considerably enriched in glycosaminoglycan-containing proteoglycans. Accumulating evidence indicates that heparan sulfate proteoglycans play a direct role in forming adhesive bonds of these cell types with the substratum whereas hyaluronic acid may function in promoting detachment of cells from the substratum. This application seeks to learn more of the biochemical complexity and the true functions of hyaluronate and proteoglycans in SAM. Various aspects of their location in SAM, intermolecular association, alteration during """"""""aging"""""""" of adhesion sites as the cell moves across the substratum generating """"""""footprints"""""""", and functional significance will be studied. Quantitative and/or qualitative changes in these moieties will also be investigated in several tumorigenic derivatives, alterations which may lead to differing adhesive behaviors of tumor cells during invasion and metastasis. Better understanding of the molecular mechanisms of adhesion to this model substratum will no doubt provide important reagents, methods, and concepts for investigating similar mechanisms of fibroblast adhesion to the much more complex extracellular matrices found in vivo.
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| Wightman, B C; Weltman, E A; Culp, L A (1986) Chondroitin sulphate proteoglycan in the substratum adhesion sites of Balb/c 3T3 cells. Fractionation on various ion-exchange and affinity columns. Biochem J 235:469-79 |
| Rosenberg, L C; Choi, H U; Poole, A R et al. (1986) Biological roles of dermatan sulphate proteoglycans. Ciba Found Symp 124:47-68 |
| Lark, M W; Laterra, J; Culp, L A (1985) Close and focal contact adhesions of fibroblasts to a fibronectin-containing matrix. Fed Proc 44:394-403 |
