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Involvement of chondroitin sulfate E in the liver tumor focal formation of murine osteosarcoma cells
| 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)
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Submitter: 山田 修平
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