Leptin enhances cell migration in human chondrosarcoma cells through OBRl leptin receptor.
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 alphavbeta3 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-kappaB (NF-kappaB) 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-kappaB cascades. Taken together, our results indicated that leptin enhances the migration of chondrosarcoma cells by increasing alphavbeta3 integrin expression through the OBR1/IRS-1/PI3K/Akt/NF-kappaB signal transduction pathway.
Yang
Shu-Ning
SN
Graduate Institute of Sports and Health, National Changhua University of Education, Changhua County 500, Taiwan.
Chen
Hsien-Te
HT
Tsou
Hsi-Kai
HK
Huang
Chun-Yin
CY
Yang
Wei-Hung
WH
Su
Chen-Ming
CM
Fong
Yi-Chin
YC
Tseng
Wen-Pei
WP
Tang
Chih-Hsin
CH
D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D002813:Chondrosarcoma / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D054411:Receptors, Leptin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D055504:Insulin Receptor Substrate Proteins; D039302:Integrin alphaVbeta3; D020738:Leptin; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D019869:Phosphatidylinositol 3-Kinases; D034741:RNA, Small Interfering; D054411:Receptors, Leptin; C526292:IRS1 protein, human; C515448:LEPR protein, human