O-Sulfated Bacterial Polysaccharides with Low Anticoagulant Activity Inhibit Metastasis

Autor: Markku Salmivirta, Anni Wärri, Anne Marjamäki, Rami Käkönen, Israel Vlodavsky, Sanna Maria Käkönen, Timo Veromaa, Benito Casu, Marjo Pihlavisto, Katri Hiilesvuo, Annamaria Naggi, Klaus Elenius, Marjut Borgenström, Giangiacomo Torri, Liisa Nissinen
Rok vydání: 2007
Předmět:
Zdroj: Seminars in Thrombosis and Hemostasis. 33:547-556
ISSN: 1098-9064
0094-6176
DOI: 10.1055/s-2007-982087
Popis: Heparin-like polysaccharides possess the capacity to inhibit cancer cell proliferation, angiogenesis, 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.
Databáze: OpenAIRE