Heparan sulfate proteoglycans from mouse mammary epithelial cells. Cell surface proteoglycan as a receptor for interstitial collagens.

J E Koda,A Rapraeger,M Bernfield

doi:10.1016/s0021-9258(17)39576-5

Abstract

A heparan sulfate-rich proteoglycan is on the surface of NMuMG mouse mammary epithelial cells apparently intercalated into their plasma membranes. Mild treatment of the cells with trypsin releases the GAG-bearing region (ectodomain) of this molecule as a discrete proteoglycan which is readily purified. At physiological pH and ionic strength, the ectodomain binds collagen types I, III, and V but not types II, IV, or denatured type I. The proteoglycan binds to a single class of high affinity saturable sites on type I collagen fibrils, sites which are selective for heparin-like glycosaminoglycans. The binding of NMuMG cells to type I collagen duplicates that of their cell surface proteoglycan; cells bind to native but not denatured collagen, and binding is inhibited by heparin but not by other glycosaminoglycans. These binding properties suggest that cell surface heparan sulfate proteoglycans could act as receptors for interstitial collagens and mediate changes in cell behavior induced by collagenous matrices.

Highlights

A heparansulfate-richproteoglycanis on the surface ectodomain’ can be released as a discrete soluble PG
Thereof NMuMG mouse mammaryepithelialcells apparently fore, we examined the collagen-binding properties of the ecintercalated into their plasma membranM es.ild treat- todomain and compared these with the collagen-binding abilment of thceells with trypsin releasesthe GAG-bearing ity of intact cells
The ectodomain and intact cells bind to native but notdenatured collagens, and this binding is inhibited by heparin-like but not other glycosaminoglycans. These characteristics suggest that the cell surface PG may bind collagen fibrils and act asa receptor to mediate the effect of the collagenous matrices on the epithelial cells

Summary

CELL SURFACE PROTEOGLYCAN AS A RECEPTOR FOR INTERSTITIAL COLLAGENS*

At physiological I1 or IV and hinds to a single class of high affinity saturable pH and ionic strength, the ectodomain binds collagen types I, 111, and V but not types 11, IV, or denatured type I. The proteoglycan bindsto a single class of high affinity saturable sites on type I collagen fibrils, sites which are selective for heparin-like glycosaminoglycans. The ectodomain and intact cells bind to native but notdenatured collagens, and this binding is inhibited by heparin-like but not other glycosaminoglycans. These characteristics suggest that the cell surface PG may bind collagen fibrils and act asa receptor to mediate the effect of the collagenous matrices on the epithelial cells. These binding properties suggest ctehlaltsurface heparansulfate proteoglycans could actas recep-

RESULTS

Cell Surface Proteoglycanas Collagen Receptor d

DISCUSSION

Our failure to show bindingtotype IV collagen under