A1 Refereed original research article in a scientific journal

O-sulfated bacterial polysaccharides with low anticoagulant activity inhibit metastasis




AuthorsBorgenstrom M, Warri A, Hiilesvuo K, Kakonen R, Kakonen S, Nissinen L, Pihlavisto M, Marjamaki A, Vlodavsky I, Naggi A, Torri G, Casu B, Verornaa T, Salmivirta M, Elenius K

PublisherTHIEME MEDICAL PUBL INC

Publication year2007

JournalSeminars in Thrombosis and Hemostasis

Journal name in sourceSEMINARS IN THROMBOSIS AND HEMOSTASIS

Journal acronymSEMIN THROMB HEMOST

Volume33

Issue5

First page 547

Last page556

Number of pages10

ISSN0094-6176

DOIhttps://doi.org/10.1055/s-2007-982087


Abstract
Heparin-like polysaccharides possess the capacity to inhibit cancer cell proliferation, anglogenesis, heparanase-mediated cancer cell invasion, and cancer cell adhesion to vascular endothelia via adhesion receptors, such as selectins. The clinical applicability of the antitumor effect of such polysaccharides, however, is compromised by their anticoagulant activity. We have compared the potential of chemically O-sulfated and N,O-sulfated bacterial polysaccharide (capsular polysaccharide from E. coli K5 [K5PS]) species to inhibit metastasis of mouse B16-BL6 melanoma cells and human MDA-MB-231 breast cancer cells in two in vivo models. We demonstrate that in both settings, O-sulfated K5PS was a potent inhibitor of metastasis. Reducing the molecular weight of the polysaccharide, however, resulted in lower antimetastatic capacity. Furthermore, we show that O-sulfated K5PS efficiently inhibited the invasion of B16-BL6 cells through Matrigel and also inhibited the in vitro activity of heparanase. Moreover, treatment with O-sulfated K5PS lowered the ability of B16-BL6 cells to adhere to endothelial cells, intercellular adhesion molecule-1, and P-selectin, but not to E-selectin. Importantly, O-sulfated K5PSs were largely devoid of anticoagulant activity. These findings indicate that O-sulfated K5PS polysaccharide should be considered as a potential antimetastatic agent.



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