A1 Refereed original research article in a scientific journal
O-sulfated bacterial polysaccharides with low anticoagulant activity inhibit metastasis
Authors: Borgenstrom 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
Publisher: THIEME MEDICAL PUBL INC
Publication year: 2007
Journal: Seminars in Thrombosis and Hemostasis
Journal name in source: SEMINARS IN THROMBOSIS AND HEMOSTASIS
Journal acronym: SEMIN THROMB HEMOST
Volume: 33
Issue: 5
First page : 547
Last page: 556
Number of pages: 10
ISSN: 0094-6176
DOI: https://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.
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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