Heparan Sulfate Proteoglycans as Adhesive and Anti-invasive Molecules

doi:10.1074/jbc.273.35.22825

Heparan Sulfate Proteoglycans as Adhesive and Anti-invasive Molecules

SYNDECANS AND GLYPICAN HAVE DISTINCT FUNCTIONS*

From the ^‡Department of Pathology and ^‖Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, the ^§Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and the ^¶Department of Developmental and Cell Biology, University of California, Irvine, California 92697

Abstract

ARH-77 cells do not adhere to type I collagen and readily invade into collagen gels, but following expression of the transmembrane heparan sulfate proteoglycan syndecan-1, they bind collagen and fail to invade. We now show that cells transfected with syndecan-2 or syndecan-4 also bind collagen and are non-invasive. In contrast, cells transfected with the glycosylphosphatidylinositol-anchored proteoglycan glypican-1 do not bind to collagen and remain invasive, even though glypican- and syndecan-expressing cells have similar surface levels of heparan sulfate, and their proteoglycans have similar affinities for collagen. Analysis of cells expressing syndecan-1-glypican-1 chimeric proteoglycans reveals that inhibition of invasion requires the extracellular domain of syndecan but not its transmembrane or cytoplasmic domain. Surprisingly, cells bearing a chimera composed of the glypican extracellular domain fused to the syndecan transmembrane and cytoplasmic domains bind to collagen but remain invasive, implying that adhesion to collagen is not by itself sufficient to inhibit invasion. Apparently, the extracellular domain of syndecan-1, presumably by interacting with cell-surface signal transducing molecules, directly regulates complex cell behaviors such as motility and invasiveness. These results also show for the first time that syndecans and glypicans can have distinct functions, even when expressed by the same cell type.

Footnotes

↵* This work was supported by National Institutes of Health Grants CA 55879, CA 68494 (to R. D. S), and NS 26862 (to A. D. L.) and National Research Service Award CA 71145 (to J. K. L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵** To whom correspondence should be addressed: Dept. of Pathology, Slot 517, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205. Tel.: 501-686-6413; Fax: 501-686-5168; E-mail: sandersonralphd{at}exchange.uams.edu.
↵2 W. Liu, M. Stanley, and R. D. Sanderson, unpublished observations.
Abbreviations:

GPI

glycosylphosphatidylinositol

PI-PLC

phosphatidylinositol phospholipase C

PBS

phosphate-buffered saline

BSA

bovine serum albumin

MOPSO

3-(N-morpholino)-2-hydroxypropanesulfonic acid

FGF

fibroblast growth factor.
- Received March 3, 1998.
- Revision received May 18, 1998.
The American Society for Biochemistry and Molecular Biology, Inc.