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Clinical & Experimental Metastasis

, Volume 16, Issue 6, pp 541–550 | Cite as

Inhibition of tumor invasion and metastasis by calciumspirulan (Ca-SP), a novel sulfated polysaccharide derived from a blue-green alga, Spirulina platensis

  • Takaaki Mishima
  • Jun Murata
  • Minako Toyoshima
  • Hideki Fujii
  • Motowo Nakajima
  • Toshimitsu Hayashi
  • Toshimitsu Kato
  • Ikuo Saiki
Article

Abstract

We have investigated the effect of calcium spirulan (Ca-SP) isolated from a blue-green alga, Spirulinaplatensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose, on inva-sionof B16-BL6 melanoma, Colon 26 M3.1 carcinoma and HT-1080 fibrosarcoma cells through reconsti-tutedbasement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells throughMatrigel/fibronectin-coated filters. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin,but it had no effect on that to fibronectin. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel andlaminin substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells withCa-SP inhibited the adhesion to laminin, while the pretreatment of laminin substrates did not. Ca-SP hadno effect on the production and activation of type IV collagenase in gelatin zymography. In contrast, Ca-SPsignificantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lungmetastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP. Seven intermittent i.v.injections of 100 mg of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in aspontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, couldreduce the lung metastasis of B16-BL6 melanoma cells, by inhibiting the tumor invasion of basementmembrane probably through the prevention of the adhesion and migration of tumor cells to laminin substrateand of the heparanase activity.©Kluwer Academic Publishers

adhesion calcium spirulan invasion laminin metastasis 

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Copyright information

© Chapman and Hall 1998

Authors and Affiliations

  • Takaaki Mishima
    • 1
  • Jun Murata
    • 1
  • Minako Toyoshima
    • 2
  • Hideki Fujii
    • 1
  • Motowo Nakajima
    • 2
  • Toshimitsu Hayashi
    • 3
  • Toshimitsu Kato
    • 4
  • Ikuo Saiki
    • 5
  1. 1.Research Institute for Wakan-YakuChibaJapan
  2. 2.Oncology ResearchTakarazuka Research Institute, Novartis Pharma K.K.Takarazuka ChibaJapan
  3. 3.Section of Chemistry, Institute of Immunological ScienceHokkaido UniversitySapporoJapan
  4. 4.Faculty of Pharmaceutical SciencesToyama Medical and Pharmaceutical UniversityToyama
  5. 5.Biochemical DivisionDainippon Ink and Chemicals, IncChibaJapan

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