Elsevier

Experimental Cell Research

Volume 228, Issue 2, 1 November 1996, Pages 283-291
Experimental Cell Research

Regular Article
Collagen VI Regulates Normal and Transformed Mesenchymal Cell Proliferationin Vitro

https://doi.org/10.1006/excr.1996.0328Get rights and content

Abstract

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 fibroblasts because they exhibit specific intracellular responses after adherence to ECM and produce large quantities of ECM proteins. Although cells cultured on different ECM proteins grew more rapidly than those on plastic, adherence and cell growth on an individual ECM protein were not correlated. To test if ECM can stimulate cell growth, soluble ECM proteins were given to cells after plating. In this culture system only collagen VI (CVI), at a concentration of 20 μg/ml in medium, increased 3T3 cell number to 402% of control by 72 h. Similar increases of human fibroblasts and HT 1080 cell numbers were noted. DNA synthesis of all three cell types increased 24 h after addition of soluble CVI. A mixture of CVI single chains, yielded by reduction and alkylation, was not stimulatory. However, this mixture efficiently inhibited the DNA synthesis induced by native CVI. Antibody inhibition studies showed that the region of CVI stimulating proliferation differs from the site bound by the integrin receptor α2β1, which mediates cell adhesion to immobilized CVI. Heparin inhibited a portion of CVI-induced proliferation. These data demonstrate that CVI can stimulate mesenchymal cell growth via a pathway that is independent of the integrin α2β1 and that the stimulatory region appears to be within the native helical portion of the collagen.

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To whom correspondence and reprint requests should be addressed at Department of Gastroenterology, Freie Universität Berlin, Universitätsklinikum Benjamin Franklin, Hindenburgdamm 30, D 12200 Berlin, Germany. Fax: 030-8445-4141.

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