Carcinogenesis Advance Access originally published online on June 23, 2009
Carcinogenesis 2009 30(10):1651-1659; doi:10.1093/carcin/bgp156
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Involvement of AdipoR receptor in adiponectin-induced motility and 
2β1 integrin upregulation in human chondrosarcoma cells
1 Graduate Institute of Clinical Medical Science, China Medical University, Taichung 404, Taiwan
2 Department of Orthopaedics, Taichung Veterans General Hospital, Taichung 407, Taiwan
3 Department of Nursing, Hungkuang University, Taichung 433, Taiwan
4 Department of Pharmacology, College of Medicine, No. 91, Hsueh-Shih Road, China Medical University, Taichung 404, Taiwan
5 Department of Orthopaedics, China Medical University Hospital, Taichung 404, Taiwan
6 Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan
* To whom correspondence should be addressed. Tel: +886 4 22053366 ext. 2228; Fax: +886 4 22053764; Email: chtang{at}mail.cmu.edu.tw
Chondrosarcoma is a type of highly malignant tumor with a capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and is involved in energy homeostasis. However, the effect of adiponectin on migration activity in human chondrosarcoma cells is mostly unknown. We found that adiponectin increased the migration and expression of 
2β1 integrin in human chondrosarcoma cells. The protein and messenger RNA expression of adiponectin receptor (AdipoR1 and AdipoR2) in chondrosarcoma patients and chondrosarcoma cell lines were significantly higher than the normal cartilage. Moreover, primary chondrosarcoma and chondrosarcoma cell lines (SW1353 and JJ012) were more invasive than normal chondrocytes. Adiponectin-mediated migration and integrin expression was attenuated by 5'-adenosine monophosphate-activated protein kinase (AMPK) small interfering RNA and an AMPK inhibitor (Ara A and compound C). Activation of p38 and nuclear factor-kappa B (NF-
B) pathways after adiponectin treatment was demonstrated, and adiponectin-induced expression of integrins and migration activity was inhibited by the specific inhibitor and mutant of p38 and NF-B cascades. This study showed for the first time that adiponectin mediates the migration of human chondrosarcoma cells. One mechanism underlying adiponectin-directed migration was transcriptional upregulation of 2β1 integrin and activation of AdipoR receptor, AMPK, p38 and NF-B pathways.
Abbreviations: AMPK, 5'-adenosine monophosphate-activated protein kinase; DN, dominant negative; IKK, IB kinase; MMP, matrix metalloproteinase; mRNA, messenger RNA; NF-B, nuclear factor-kappa B; PBS, phosphate-buffered saline; PDTC, pyrrolidine dithiocarbamate; qPCR, quantitative real-time polymerase chain reaction; siRNA, small interfering RNA; TPCK, N-tosylphenylalanyl-chloromethyl-ketone
Received January 12, 2009; revised May 10, 2009; accepted June 16, 2009.