HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 38, 28164-28174, September 21, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/38/28164    most recent M609812200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Munesue, S. Articles by Oguri, K. Search for Related Content PubMed PubMed Citation Articles by Munesue, S. Articles by Oguri, K. Social Bookmarking                      What's this?

A Novel Function of Syndecan-2, Suppression of Matrix Metalloproteinase-2 Activation, Which Causes Suppression of Metastasis^*

Seiichi Munesue, Yasuo Yoshitomi, Yuri Kusano, Yoshie Koyama, Akiko Nishiyama, Hayao Nakanishi^¶, Kaoru Miyazaki^||, Takeshi Ishimaru^**, Shuichi Miyaura^**, Minoru Okayama, and Kayoko Oguri¹

From the Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kyoto 603-8555, the Clinical Research Center, National Hospital Organization Nagoya Medical Center, 4-1-1 Sannomaru, Nakaku, Nagoya 460-0001, the ^¶Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya 464-8681, the ^||Kihara Institute for Biological Research, Yokohama City University, Yokohama 244-0813, and the ^**Central Research Laboratories, Seikagaku Corporation, Tokyo 207-0021, Japan

The syndecans comprise a family of cell surface heparan sulfate proteoglycans exhibiting complex biological functions involving the interaction of heparan sulfate side chains with a variety of soluble and insoluble heparin-binding extracellular ligands. Here we demonstrate an inverse correlation between the expression level of syndecan-2 and the metastatic potential of three clones derived from Lewis lung carcinoma 3LL. This correlation was proved to be a causal relationship, because transfection of syndecan-2 into the higher metastatic clone resulted in the suppression of both spontaneous and experimental metastases to the lung. Although the expression levels of matrix metalloproteinase-2 (MMP-2) and its cell surface activators, such as membrane-type 1 matrix metalloproteinase and tissue inhibitor of metalloproteinase-2, were similar regardless of the metastatic potentials of the clones, elevated activation of MMP-2 was observed in the higher metastatic clone. Removal of heparan sulfate from the cell surface of low metastatic cells by treatment with heparitinase-I promoted MMP-2 activation, and transfection of syndecan-2 into highly metastatic cells suppressed MMP-2 activation. Furthermore, transfection of mutated syndecan-2 lacking glycosaminoglycan attachment sites into highly metastatic cells did not have any suppressive effect on MMP-2 activation, suggesting that this suppression was mediated by the heparan sulfate side chains of syndecan-2. Actually, MMP-2 was found to exhibit a strong binding ability to heparin, the dissociation constant value being 62 nM. These results indicate a novel function of syndecan-2, which acts as a suppressor for MMP-2 activation, causing suppression of metastasis in at least the metastatic system used in the present study.

Received for publication, October 18, 2006 , and in revised form, June 25, 2007.

^* This work was supported in part by Ministry of Education, Culture, Sports, Science and Technology of Japan Grant-in-Aid for Scientific Research on Priority Areas 17046028 (to K. O.) and the "Academic Frontier" Project for Private Universities matching fund subsidy (to M. O.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 81-52-951-1111; Fax: 81-52-951-9075; E-mail: ogurik{at}nnh.hosp.go.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Basappa, S. Murugan, K. N Sugahara, C. M. Lee, G. B ten Dam, T. H van Kuppevelt, M. Miyasaka, S. Yamada, and K. Sugahara Involvement of chondroitin sulfate E in the liver tumor focal formation of murine osteosarcoma cells Glycobiology, July 1, 2009; 19(7): 735 - 742. [Abstract] [Full Text] [PDF]

				F. Li, G. B. ten Dam, S. Murugan, S. Yamada, T. Hashiguchi, S. Mizumoto, K. Oguri, M. Okayama, T. H. van Kuppevelt, and K. Sugahara Involvement of Highly Sulfated Chondroitin Sulfate in the Metastasis of the Lewis Lung Carcinoma Cells J. Biol. Chem., December 5, 2008; 283(49): 34294 - 34304. [Abstract] [Full Text] [PDF]