Basement-membrane heparan sulphate with high affinity for antithrombin synthesized by normal and transformed mouse mammary epithelial cells

Abstract

Basement-membrane proteoglycans, biosynthetically labelled with [35S]sulphate, were isolated from normal and transformed mouse mammary epithelial cells. Proteoglycans synthesized by normal cells contained mainly heparan sulphate and, in addition, small amounts of chondroitin sulphate chains, whereas transformed cells synthesized a relatively higher proportion of chondroitin sulphate. Polysaccharide chains from transformed cells were of lower average Mr and of lower anionic charge density compared with chains isolated from the untransformed counterparts, confirming results reported previously [David & Van den Berghe (1983) J. Biol. Chem. 258, 7338-7344]. A large proportion of the chains isolated from normal cells bound with high affinity to immobilized antithrombin, and the presence of 3-O-sulphated glucosamine residues, previously identified as unique markers for the antithrombin-binding region of heparin [Lindahl, Bäckström, Thunberg & Leder (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 6551-6555], could be demonstrated. A significantly lower proportion of the chains derived from transformed cells bound with high affinity to antithrombin, and a corresponding decrease in the amount of incorporated 3-O-sulphate was observed.

The Putative Tumor Suppressors EXT1 and EXT2 Are Glycosyltransferases Required for the Biosynthesis of Heparan Sulfate

“…A mutation in the appropriate EXT protein might affect such interaction as well as the initial polymerization reaction itself, with presently unpredictable effects on the structure of the final product. Indeed, many different types of tumors are associated with distinct changes in glycosaminoglycan, particularly HS, structure (23)(24)(25)(26)(27). Although the mechanisms behind these changes are generally unknown, the alterations may be expected to affect functional interactions with a variety of proteins that are potentially involved in neoplastic transformation.…”

Expression of Heparan Sulfate d-Glucosaminyl 3-O-Sulfotransferase Isoforms Reveals Novel Substrate Specificities

“…7 Furthermore, 3-OST-2 should sulfate the sequence containing GlcA2S with much higher efficiency because the population of a sulfated glucuronic acid is approximately 5-50-fold less frequent than that of a sulfated iduronic acid in any given heparan sulfate (35)(36)(37)(38). Our Northern analysis has demonstrated that 3-OST-2 is predominantly expressed in human brain as described in the accompanying article (24).…”

Structural Requirements of Heparan Sulfate for the Binding to the Tumor-derived Adhesion Factor/Angiomodulin That Induces Cord-like Structures to ECV-304 Human Carcinoma Cells

“…The HS-GAGs show distinct alterations in sulfation patterns, total chain length, and the number of sulfated domains. A number of earlier studies have indicated malignancy-associated undersulfation of cell surface HS (43)(44)(45). Recent detailed structural analysis has revealed the specific structural changes of HS isolated from human adenoma and carcinoma cells during the colon carcinogenesis (46).…”