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

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Title: Involvement of chondroitin sulfate E in the liver tumor focal formation of murine osteosarcoma cells
Authors: Basappa Browse this author
Murugan, Sengottuvelan Browse this author
Sugahara, Kazuki N. Browse this author →KAKEN DB
Lee, Chun Man Browse this author
ten Dam, Gerdy B. Browse this author
van Kuppevelt, Toin H. Browse this author
Miyasaka, Masayuki Browse this author
Yamada, Shuhei Browse this author
Sugahara, Kazuyuki Browse this author
Keywords: chondroitin sulfate
glycosaminoglycan
tumor
osteosarcoma
sulfation
Issue Date: Jul-2009
Publisher: Oxford University Press
Journal Title: Glycobiology
Volume: 19
Issue: 7
Start Page: 735
End Page: 742
Publisher DOI: 10.1093/glycob/cwp041
PMID: 19293233
Abstract: 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.
Rights: 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: http://dx.doi.org/10.1093/glycob/cwp041
Type: article (author version)
URI: http://hdl.handle.net/2115/43174
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 山田 修平

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