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Carcinogenesis Advance Access published online on January 23, 2009
Carcinogenesis, doi:10.1093/carcin/bgp023
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Leptin enhances cell migration in human chondrosarcoma cells through OBRl leptin receptor

Shu-Ning Yang1,2, Hsien-Te Chen4,7, Hsi-Kai Tsou3,10,7, Chun-Yin Huang8, Wei-Hung Yang8,5, Chen Ming Su1,2, Yi-Chin Fong4,5,6,*, Wen-Pei Tseng1,* and Chih-Hsin Tang2,9,*

1 Graduate Institute of Sports and Health, National Changhua University of Education, Changhua County, Taiwan
2 Department of Pharmacology, China Medical University, Taichung, Taiwan
3 Department of Neurosurgery, Taichung Veterans General Hospital, Taichung Taiwan
4 Department of Orthopaedics, China Medical University Hospital, Taichung, Taiwan
5 School of Chinese Medicine, China Medical University, Taichung, Taiwan
6 Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan
7 Department of Materials Science and Engineering, Feng Chia University, Taichung, Taiwan
8 Department of Orthopaedic, China Medical University Beigang Hospital, Yun-Lin County, Taiwan
9 Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
10 Center for General Education, Jen-Teh Junior College of Medicine, Miaoli County, Taiwan

* Author for Correspondence: Tang Chih-Hsin, Department of Pharmacology, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, Taiwan, Tel: (886) 4-22053366 Ext. 2228. Fax: (886) 4-22053764. E-mail: chtang{at}mail.cmu.edu.tw Or Tseng Wen-Pei; E-mail: twp{at}cc.ncue.edu.tw and Fong Yi-Chin; E-mail: yichin{at}mail.cmu.edu.tw

Leptin, an adipocyte-derived cytokine that is closely associated with obesity, has recently been shown to be involved in carcinogenesis and cancer progression. Integrins are the major adhesive molecules in mammalian cells, and have been associated with metastasis of cancer cells. In this study, we found that leptin increased the migration and the expression of {alpha}vβ3 integrin in human chondrosarcoma cells. We also found that human chondrosarcoma tissues and chondrosarcoma cell lines had significant expression of the long form (OBRl) leptin receptor, which was higher than that in normal cartilage and human primary chondrocyte. Leptin-mediated migration and integrin up-regulation was attenuated by OBRl receptor antisense oligonucleotide. Activations of IRS-1 (insulin receptor substrate), phosphatidylinositol 3-kinase (PI3K), Akt and NF-{kappa}B pathways after leptin treatment was demonstrated, and leptin-induced expression of integrin and migration activity was inhibited by the specific inhibitor, siRNA and mutant of IRS-1, PI3K, Akt and NF-{kappa}B cascades. Taken together, our results indicated that leptin enhances the migration of chondrosarcoma cells by increasing {alpha}vβ3 integrin expression through the OBR1/IRS-1/PI3K/Akt/NF-{kappa}B signal transduction pathway.

Key Words: Leptin • Chondrosarcoma • OBRl • Integirn

S.-N. Yang, H.-T. Chen and H.-K. Tsou contributed equally to this study.

Received September 5, 2008; revised January 7, 2009; accepted January 11, 2009.


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