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Title
  • Receptor for Advanced Glycation End Products (RAGE) Functions as a Receptor for Specific Sulfated Glycosaminoglycans, and Anti-RAGE Antibody or The Sulfated Glycosaminoglycans Delivered in Vivo Inhibit Pulmonary Metastasis of Tumor Cells
Creator

Shuji, Mizumoto

Jun, Takahashi

Kazuyuki, Sugahara

Rights
    • This research was originally published in JOURNAL OF BIOLOGICAL CHEMISTRY. : Shuji MIZUMOTO, Jun TAKAHASHI, Kazuyuki SUGAHARA. Receptor for Advanced Glycation End Products (RAGE) Functions as a Receptor for Specific Sulfated Glycosaminoglycans, and Anti-RAGE Antibody or The Sulfated Glycosaminoglycans Delivered in vivo Inhibit Pulmonary Metastasis of Tumor Cells. 2012; Vol.287(23) :18985-18994. © 2012 the American Society for Biochemistry and Molecular Biology.
Subject
  • NDC 490
Description
Other
  • Altered expression of chondroitin sulfate (CS) and heparan sulfate (HS) at the surfaces of tumor cells plays a key role in malignant transformation and tumor metastasis. Previously we demonstrated that a Lewis lung carcinoma (LLC)-derived tumor cell line with high metastatic potential had a higher proportion of E-disaccharide units, GlcUA-GalNAc(4,6-O-disulfate), in CS chains than low metastatic LLC cells and that such CS chains are involved in the metastatic process. The metastasis was markedly inhibited by the pre-administration of CS-E from squid cartilage rich in E units or by preincubation with a phage display antibody specific for CS-E. However, the molecular mechanism of the inhibition remains to be investigated. In this study the receptor molecule for CS chains containing E-disaccharides expressed on LLC cells was revealed to be receptor for advanced glycation end products (RAGE), which is a member of the immunoglobulin superfamily predominantly expressed in the lung. Interestingly, RAGE bound strongly to not only E-disaccharide, but also HS-expressing LLC cells. Furthermore, the colonization of the lungs by LLC cells was effectively inhibited by the blocking of CS or HS chains at the tumor cell surface with an anti-RAGE antibody through intravenous injections in a dose-dependent manner. These results provide the clear evidence that RAGE is at least one of the critical receptors for CS and HS chains expressed at the tumor cell surface and involved in experimental lung metastasis and that CS/HS and RAGE are potential molecular targets in the treatment of pulmonary metastasis.
PublisherAmerican Society for Biochemistry and Molecular Biology
Date Issued 2012-06-01
Languageeng
NIItypejournal article
VersiontypeAM
Identifier URI http://hdl.handle.net/2115/49329
Relation
  • isIdenticalTo DOI https://doi.org/10.1074/jbc.M111.313437
Journal
    • ISSN 0021-9258
    • ISSN 1083-351X
    • The Journal of Biological Chemistry
    287(23), 18985-18994
File
Oaidate2019-10-09T00:14:31Z