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Heparan/Chondroitin/Dermatan Sulfate Primer 2-(6-Hydroxynaphthyl)-O-ß-D-Xylopyranoside Preferentially Inhibits Growth of Transformed Cells¹

Department of Cell Biology and Molecular Biology, Lund University, S-221 00 Lund, Sweden [K. M., B. H., S. P., A. M., G. W-T., L-Å. F.]; Tokyo Research Institute, Seikagaku Corp., 103 Tokyo, Japan [Y. K., H. Y., K. S.]; and Institute for Molecular Science of Medicine, Aichi Medical University; 480-11 Aichi, Japan [S. A., H. H., S. S., K. K.]

Xylose forms the direct carbohydrate-protein link in extra- or pericellular proteoglycans (PGs) that are substituted with either chondroitin sulfate (CS)/dermatan sulfate (DS) and/or heparan sulfate (HS). Cell surface PGs carrying HS are important regulators of cell growth. Xylose coupled to an aromatic compound can enter cells and initiate either CS/DS synthesis or both HS and CS/DS synthesis, depending on the nature of the aromatic adduct. Here, we show that 2-(6-hydroxynaphthyl)-O-ß-D-xylopyranoside, which can prime both types of glycan chains, inhibits growth of a set of normal and transformed cells. Transformed cells are preferentially inhibited, and at a concentration of 0.15–0.20 mM xyloside, transformed cells are totally growth arrested, whereas normal cells are only 50% inhibited. No inhibition of growth is observed with the stereoisomeric 2-(6-hydroxynaphthyl)-O-ß-L-xylopyranoside, which does not prime glycosaminoglycan synthesis at all; with the nonhydroxylated 2-naphthyl-O-ß-D-xylopyranoside, which only primes CS/DS synthesis under these conditions; or with p-nitrophenyl-O-ß-D-xylopyranoside, which is known to prime only CS/DS synthesis. We conclude that growth inhibition is due to priming of HS and/or CS/DS synthesis, which may either lead to the formation of specific antiproliferative glycans or glycan fragments or to interference with endogenous PG synthesis and turnover.

¹ This work was supported by the Swedish Medical Research Council, the Swedish Cancer Fund, the G. A. E. Nilsson Foundation, and the J. A. Persson Foundation.

² To whom requests for reprints should be addressed, at Department of Cell and Molecular Biology, P.O. Box 94, S-221 00 Lund, Sweden. Phone: 46 46 222 8573; Fax: 46 46 222 3128; E-mail: Katrin.Mani@medkem.lu.se.

Received 11/ 6/97. Accepted 1/29/98.

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