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J. Biol. Chem., Vol. 278, Issue 16, 14321-14330, April 18, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/16/14321    most recent M212246200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lauer-Fields, J. L. Articles by Fields, G. B. Search for Related Content PubMed PubMed Citation Articles by Lauer-Fields, J. L. Articles by Fields, G. B. Social Bookmarking                      What's this?

Melanoma Cell CD44 Interaction with the 1(IV)1263-1277 Region from Basement Membrane Collagen Is Modulated by Ligand Glycosylation^*

Janelle L. Lauer-Fields, Navdeep B. Malkar^§, Gérard Richet^¶, Karlheinz Drauz, and Gregg B. Fields^**

From the  Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, Florida 33431-0991, ^¶ Degussa/Rexim SA, 33 Rue de Verdun, F-80400 HAM, France, and  Degussa AG, Rodenbacher Chaussee 4, D-63457 Hanau-Wolfgang, Germany

Invasion of the basement membrane is believed to be a critical step in the metastatic process. Melanoma cells have been shown previously to bind distinct triple-helical regions within basement membrane (type IV) collagen. Additionally, tumor cell binding sites within type IV collagen contain glycosylated hydroxylysine residues. In the present study, we have utilized triple-helical models of the type IV collagen 1(IV)1263-1277 sequence to (a) determine the melanoma cell receptor for this ligand and (b) analyze the results of single-site glycosylation on melanoma cell recognition. Receptor identification was achieved by a combination of methods, including (a) cell adhesion and spreading assays using triple-helical 1(IV)1263-1277 and an Asp¹²⁶⁶Abu variant, (b) inhibition of cell adhesion and spreading assays, and (c) triple-helical 1(IV)1263-1277 affinity chromatography with whole cell lysates and glycosaminoglycans. Triple-helical 1(IV)1263-1277 was bound by melanoma cell CD44/chondroitin sulfate proteoglycan receptors and not by the collagen-binding integrins or melanoma-associated proteoglycan. Melanoma cell adhesion to and spreading on the triple-helical 1(IV)1263-1277 sequence was then compared for glycosylated (replacement of Lys¹²⁶⁵ with Hyl(O--D-galactopyranosyl)) versus non-glycosylated ligand. Glycosylation was found to strongly modulate both activities, as adhesion and spreading were dramatically decreased due to the presence of galactose. CD44/chondroitin sulfate proteoglycan did not bind to glycosylated 1(IV)1263-1277. Overall, this study (a) is the first demonstration of the prophylactic effects of glycosylation on tumor cell interaction with the basement membrane, (b) provides a rare example of an apparent unfavorable interaction between carbohydrates, and (c) suggests that sugars may mask "cryptic sites" accessible to tumor cells with cell surface or secreted glycosidase activities.

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