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Involvement of AdipoR receptor in adiponectin-induced motility and α2β1 integrin upregulation in human chondrosarcoma cells
被引:37
作者:
Chiu, Yung-Cheng
[2
,3
,4
]
Shieh, Dong-Chen
[4
]
Tong, Kwok-Man
[3
]
Chen, Chao-Ping
[3
]
Huang, Kui-Chou
[3
]
Chen, Po-Chun
[1
]
Fong, Yi-Chin
[5
]
Hsu, Horng-Chang
[2
,5
]
Tang, Chih-Hsin
[1
,6
]
机构:
[1] China Med Univ, Dept Pharmacol, Coll Med, Taichung 404, Taiwan
[2] China Med Univ, Grad Inst Clin Med Sci, Taichung 404, Taiwan
[3] Taichung Vet Gen Hosp, Dept Orthopaed, Taichung 407, Taiwan
[4] Hungkuang Univ, Dept Nursing, Taichung 433, Taiwan
[5] China Med Univ Hosp, Dept Orthopaed, Taichung 404, Taiwan
[6] China Med Univ, Grad Inst Basic Med Sci, Taichung 404, Taiwan
关键词:
ACTIVATED PROTEIN-KINASE;
NF-KAPPA-B;
SERUM ADIPONECTIN;
GLUCOSE-TRANSPORT;
PROGNOSTIC VALUE;
PROSTATE-CANCER;
EXPRESSION;
BETA-1-INTEGRIN;
STIMULATION;
ASSOCIATION;
D O I:
10.1093/carcin/bgp156
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
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 alpha 2 beta 1 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-kappa 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-kappa 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 alpha 2 beta 1 integrin and activation of AdipoR receptor, AMPK, p38 and NF-kappa B pathways.
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页码:1651 / 1659
页数:9
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