In:
Journal of Cell Science, The Company of Biologists, Vol. 113, No. 23 ( 2000-12-01), p. 4287-4299
Abstract:
Many aspects of cell behavior are regulated by cell-extracellular matrix interactions, including cell migration and cell growth. We previously showed that the addition of soluble fibronectin to collagen-adherent fibronectin-null cells enhances cell growth. This growth-promoting effect of fibronectin depended upon the deposition of fibronectin into the extracellular matrix; occupancy and clustering of fibronectin-binding integrins was not sufficient to trigger enhanced cell growth. To determine whether the binding of integrins to fibronectin’s RGD site is required for fibronectin-enhanced cell growth, the ability of fibronectin lacking the integrin-binding RGD site (FNΔRGD) to promote cell growth was tested. FNΔRGD promoted cell growth when used as an adhesive substrate or when added in solution to collagen-adherent fibronectin-null cells. Addition of FNΔRGD to collagen-adherent fibronectin-null cells resulted in a 1.6-1.8× increase in cell growth in comparison with cells grown in the absence of fibronectin. The growth-promoting effects of FNΔRGD and wild-type fibronectin were blocked by inhibitors of fibronectin polymerization, including the anti-fibronectin antibody, L8. In addition, FNΔRGD-induced cell growth was completely inhibited by the addition of heparin, and was partially blocked by either heparitinase-treatment or by addition of recombinant fibronectin heparin-binding domain. Heparin and heparitinase-treatment also partially blocked the growth-promoting effects of wild-type fibronectin, as well as the deposition of wild-type fibronectin into the extracellular matrix. These data suggest that cell surface heparan-sulfate proteoglycans contribute to the growth-promoting effects of FNΔRGD and wild-type fibronectin. Addition of heparin, treatment with heparitinase, or incubation with monoclonal antibody L8 all inhibited the formation of short linear FNΔRGD fibrils on the cell surface. Inhibitory β1 integrin antibodies had no effect on FNΔRGD fibril formation, FNΔRGD-induced cell growth, or cell adhesion on FNΔRGD-coated substrates. These data suggest that fibronectin fibril formation can promote cell growth by a novel mechanism that is independent of RGD-integrin binding, and that involves cell surface proteoglycans.
Type of Medium:
Online Resource
ISSN:
0021-9533
,
1477-9137
DOI:
10.1242/jcs.113.23.4287
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2000
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
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