title: Regulatory effects of Spirulina complex polysaccharides on growth of murine RSV-M glioma cells through Toll-like receptor 4.
abstract: This study is the first to report that Spirulina complex polysaccharides (CPS) suppress glioma growth by down-regulating angiogenesis via a Toll-like receptor 4 signal. Murine RSV-M glioma cells were implanted s.c. into C3H/HeN mice and TLR4 mutant C3H/HeJ mice. Treatment with either Spirulina CPS or Escherichia coli (E. coli) lipopolysaccharides (LPS) strongly suppressed RSV-M glioma cell growth in C3H/HeN, but not C3H/HeJ, mice. Glioma cells stimulated production of interleukin (IL)-17 in both C3H/HeN and C3H/HeJ tumor-bearing mice. Treatment with E. coli LPS induced much greater IL-17 production in tumor-bearing C3H/HeN mice than in tumor-bearing C3H/HeJ mice. In C3H/HeN mice, treatment with Spirulina CPS suppressed growth of re-transplanted glioma; however, treatment with E. coli LPS did not, suggesting that Spirulina CPS enhance the immune response. Administration of anti-cluster of differentiation (CD)8, anti-CD4, anti-CD8 antibodies, and anti-asialo GM1 antibodies enhanced tumor growth, suggesting that T cells and natural killer cells or macrophages are involved in suppression of tumor growth by Spirulina CPS. Although anti-interferon-γ antibodies had no effect on glioma cell growth, anti-IL-17 antibodies administered four days after tumor transplantation suppressed growth similarly to treatment with Spirulina CPS. Less angiogenesis was observed in gliomas from Spirulina CPS-treated mice than in those from saline- or E. coli LPS-treated mice. These findings suggest that, in C3H/HeN mice, Spirulina CPS antagonize glioma cell growth by down-regulating angiogenesis, and that this down-regulation is mediated in part by regulating IL-17 production.
authors.affiliation: Department of Neurosurgery, Kochi Medical School, Kohasu, Okoh-cho, Nankoku, Kochi 7838505 Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kawanishi
authors.forename: Akira
authors.initials: A
authors.lastname: Tominaga
authors.forename: Hiromi
authors.initials: H
authors.lastname: Okuyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuoka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taguchi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kusumoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Yawata
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Shiro
authors.initials: S
authors.lastname: Ono
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000378:metabolism*; D045744:Cell Line, Tumor; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D007155:Immunologic Factors / Q000276:immunology* / Q000302:isolation & purification; D020381:Interleukin-17 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000302:isolation & purification; D053545:Spirulina / Q000737:chemistry*; D013601:T-Lymphocytes / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors; D020381:Interleukin-17; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4