Semin Thromb Hemost 2007; 33(5): 547-556
DOI: 10.1055/s-2007-982087
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

O-Sulfated Bacterial Polysaccharides with Low Anticoagulant Activity Inhibit Metastasis

Marjut Borgenström1 , Anni Wärri1 , Katri Hiilesvuo1 , Rami Käkönen2 , Sanna Käkönen2 , Liisa Nissinen3 , Marjo Pihlavisto3 , Anne Marjamäki3 , Israel Vlodavsky4 , Annamaria Naggi5 , Giangiacomo Torri5 , Benito Casu5 , Timo Veromaa3 , Markku Salmivirta1 , Klaus Elenius6
  • 1Turku Centre for Biotechnology, University of Turku, and Åbo Akademi University, Turku, Finland
  • 2Pharmatest Services Ltd., Turku, Finland
  • 3BioTie Therapies Corp., Turku, Finland
  • 4Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
  • 5Institute for Chemical and Biochemical Research “G. Ronzoni,” Milan, Italy
  • 6Medicity Research Laboratory, and Department of Medical Biochemistry and Molecular Biology, University of Turku, and Department of Oncology, Turku University Hospital, Turku, Finland
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Publikationsdatum:
16. Juli 2007 (online)

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ABSTRACT

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.

REFERENCES

Dr. Klaus Elenius

Department of Medical Biochemistry and Molecular Biology

University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland

eMail: klaus.elenius@utu.fie