Journal Article

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

Shu-Ning Yang, Hsien-Te Chen, Hsi-Kai Tsou, Chun-Yin Huang, Wei-Hung Yang, Chen-Ming Su, Yi-Chin Fong, Wen-Pei Tseng and Chih-Hsin Tang

in Carcinogenesis

Volume 30, issue 4, pages 566-574
Published in print April 2009 | ISSN: 0143-3334
Published online January 2009 | e-ISSN: 1460-2180 | DOI:
Leptin enhances cell migration in human chondrosarcoma cells through OBRl leptin receptor

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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 αvβ3 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 upregulation were attenuated by OBRl receptor antisense oligonucleotide. Activations of insulin receptor substrate (IRS)-1, phosphatidylinositol 3-kinase (PI3K), Akt and nuclear factor-κB (NF-κB) pathways after leptin treatment were demonstrated, and leptin-induced expression of integrin and migration activity was inhibited by the specific inhibitor, small-interfering RNA and mutant of IRS-1, PI3K, Akt and NF-κB cascades. Taken together, our results indicated that leptin enhances the migration of chondrosarcoma cells by increasing αvβ3 integrin expression through the OBR1/IRS-1/PI3K/Akt/NF-κB signal transduction pathway.

Journal Article.  5202 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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