title: Involvement of AdipoR receptor in adiponectin-induced motility and alpha2beta1 integrin upregulation in human chondrosarcoma cells.
abstract: 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 alpha2beta1 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-kappaB) 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-kappaB 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 alpha2beta1 integrin and activation of AdipoR receptor, AMPK, p38 and NF-kappaB pathways.
authors: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors: Yung-Cheng
authors: YC
authors: Chiu
authors: Dong-Chen
authors: DC
authors: Shieh
authors: Kwok-Man
authors: KM
authors: Tong
authors: Chao-Ping
authors: CP
authors: Chen
authors: Kui-Chou
authors: KC
authors: Huang
authors: Po-Chun
authors: PC
authors: Chen
authors: Yi-Chin
authors: YC
authors: Fong
authors: Horng-Chang
authors: HC
authors: Hsu
authors: Chih-Hsin
authors: CH
authors: Tang
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D052242:Adiponectin / Q000502:physiology; D002358:Cartilage, Articular / Q000166:cytology; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology; D002813:Chondrosarcoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D038982:Integrin alpha2beta1 / Q000235:genetics*; D016328:NF-kappa B / Q000502:physiology; D009361:Neoplasm Invasiveness; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D054419:Receptors, Adiponectin / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D038982:Integrin alpha2beta1; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; D011494:Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases