Over-sulfated glycosaminoglycans are alternative selectin ligands: insights into molecular interactions and possible role in breast cancer metastasis.

We report herein that cancer-associated GAGs are differentially recognized by selectins according to their density of sulfation and the pH conditions of the binding. We also show that these parameters regulate platelets-cancer cells heterotypic aggregation, supporting the idea that GAGs may have pro-metastatic function. Combining our experimental results with in depth analyses of molecular dockings, we propose a model of GAG/selectin interactions robust enough to recapitulate the differential binding of selectins to GAGs, the competition between GAGs and sLe(x) for selectin binding and the effect of sub-physiological pH on GAGs affinities towards selectins. Altogether, our data suggest GAGs to be good ligands for selectins, potentially promoting distant metastasis in a complementary way to sLe(x).
PMID: 23739843 [PubMed - as supplied by publisher]

Source: Clinical Breast Cancer - June 6, 2013 Category: Cancer & Oncology Authors: Martinez P, Vergoten G, Colomb F, Bobowski M, Steenackers A, Carpentier M, Allain F, Delannoy P, Julien S Tags: Clin Exp Metastasis Source Type: research