COLLAGEN-VI REGULATES NORMAL AND TRANSFORMED MESENCHYMAL CELL-PROLIFERATION IN-VITRO

Suggestions exist that, in addition to traditional growth factors, the extracellular matrix (ECM) of a cell can regulate its proliferation. This hypothesis was investigated with normal and transformed fibroblas ts because they exhibit specific intracellular responses after adheren ce to ECM and produce large quantities of ECM proteins. Although cells cultured on different ECM proteins grew more rapidly than those on pl astic, adherence and cell growth on an individual ECM, protein were no t correlated. To test if ECM can stimulate cell growth, soluble ECM pr oteins were given to cells after plating. In this culture system only collagen VI (CVI), at a concentration of 20 mu g/ml in medium, increas ed 3T3 cell number to 402% of control by 72 h. Similar increases of hu man fibroblasts and HT 1080 cell numbers were noted. DNA synthesis of all three cell types increased 24 h after addition of soluble CVI. A m ixture of CVI single chains, yielded by reduction and alkylation, was not stimulatory. However, this mixture efficiently inhibited the DNA s ynthesis induced by native CVI. Antibody inhibition studies showed tha t the region of CVI stimulating proliferation differs from the site bo und by the integrin receptor alpha 2 beta 1, which mediates cell adhes ion to immobilized CVI. Heparin inhibited a portion of CVI-induced pro liferation. These data demonstrate that CVI can stimulate mesenchymal cell growth via a pathway that is independent of the integrin alpha 2 beta 1 and that the stimulatory region appears to be within the native helical portion of the collagen. (C) 1996 Academic Press, Inc.