• Involvement of chondroitin sulfate E in the liver tumor focal formation of murine osteosarcoma cells


Murugan, Sengottuvelan

Sugahara, Kazuki N.

Lee, Chun Man

ten Dam, Gerdy B.

van Kuppevelt, Toin H.

Miyasaka, Masayuki

Yamada, Shuhei

Sugahara, Kazuyuki

    • This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Glycobiology following peer review. The definitive publisher-authenticated version 19(7):735-742, July 2009 is available online at:
  • Other chondroitin sulfate
  • Other glycosaminoglycan
  • Other tumor
  • Other osteosarcoma
  • Other sulfation
  • NDC 494
  • Cell surface heparan sulfate plays a critical role in regulating the metastatic behavior of tumor cells, whereas the role of chondroitin sulfate/dermatan sulfate (CS/DS) has been little understood in this context. Here, we characterized CS/DS chains from the murine osteosarcoma cell line LM8G7, which forms tumor nodules in liver. Structural analysis of the CS/DS chains showed a higher proportion of GlcUAβ1-3GalNAc(4,6-O-disulfate) (E-units) in LM8G7 (12%) than in its parental cell line LM8 (6%), which rarely forms tumors in the liver. Immunostaining with GD3G7, an antibody specific to E-units, confirmed the higher expression of the epitope in LM8G7 than LM8 cells. The tumor focal formation of LM8G7 cells in the liver in mice was effectively inhibited by the pre-administration of CS-E (rich in E-unit) or the pre-incubation of the antibody GD3G7 with the tumor cells. CS-E or GD3G7 inhibited the adhesion of LM8G7 cells to a laminin-coated plate in vitro. In addition, the invasive ability of LM8G7 cells in vitro was also reduced by the addition of CS-E or the antibody. Further, CS-E or the antibody inhibited the proliferation of LM8G7 cells dose-dependently. The binding of LM8G7 cells to VEGF in vitro was also significantly reduced by CS-E and GD3G7. Thus, the present study reveals the significance of highly sulfated CS/DS structures in the liver colonization of osteosarcoma cells and also provides a framework for the development of GAG-based anti-cancer molecules.
PublisherOxford University Press
Date Issued 2009-07
NIItypejournal article
Identifier URI
  • isIdenticalTo PMID 19293233
  • isIdenticalTo DOI
    • ISSN 0959-6658
    • Glycobiology
    19(7), 735-742