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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
| 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 |
| Authors: | Shuji, Mizumoto Browse this author →KAKEN DB | | Jun, Takahashi Browse this author | | Kazuyuki, Sugahara Browse this author →KAKEN DB |
| Issue Date: | 1-Jun-2012 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Journal Title: | The Journal of Biological Chemistry |
| Volume: | 287 |
| Issue: | 23 |
| Start Page: | 18985 |
| End Page: | 18994 |
| Publisher DOI: | 10.1074/jbc.M111.313437 |
| Abstract: | 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. |
| 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. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/49329 |
| 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: 菅原 一幸
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