Chondrosarcoma is the second most frequently occurring type of bone malignancy characterized by distant metastatic propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumour lymphangiogenesis and lymphatic metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. In recent years, adiponectin has also been indicated as facilitating tumorigenesis, angiogenesis and metastasis. However, the effect of adiponectin on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has remained largely a mystery. In the present study, we have shown a clinical correlation between adiponectin and VEGF-C, as well as tumour stage, in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knock down inhibited lymphangiogenesis in vitro and in vivo. We also found that adiponectin-induced VEGF-C is mediated by the calmodulin-dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK) and p38 signaling pathway. Furthermore, the expression of miR-27b was negatively regulated by adiponectin via the CaMKII, AMPK and p38 cascade. The present study is the first to describe the mechanism of adiponectin-promoted lymphangiogenesis by up-regulating VEGF-C expression in chondrosarcomas. Thus, adiponectin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis.
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September 2016
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Corin protein expression in human renal proximal convoluted tubules as shown by brown staining in immunohistochemistry. See pp. 1655-1664 for further details. Image kindly provided by Qingyu Wu.
Research Article|
July 18 2016
Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells
Chun-Yin Huang;
Chun-Yin Huang
1
*Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yunlin County, Taiwan
†School of Medicine, China Medical University, Taichung, Taiwan
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An-Chen Chang;
An-Chen Chang
1
††Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
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Hsien-Te Chen;
Hsien-Te Chen
§Department of Orthopaedic Surgery, China Medical University Hospital, Taichung, Taiwan
║School of Chinese Medicine, China Medical University, Taichung, Taiwan
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Shih-Wei Wang;
Shih-Wei Wang
¶Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
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Yuan-Shun Lo;
Yuan-Shun Lo
*Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yunlin County, Taiwan
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Chih-Hsin Tang
†School of Medicine, China Medical University, Taichung, Taiwan
**Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
‡Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
Correspondence:C.-H. Tang (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 16 2016
Revision Received:
May 26 2016
Accepted:
June 01 2016
Accepted Manuscript online:
June 01 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (17): 1523–1533.
Article history
Received:
February 16 2016
Revision Received:
May 26 2016
Accepted:
June 01 2016
Accepted Manuscript online:
June 01 2016
Citation
Chun-Yin Huang, An-Chen Chang, Hsien-Te Chen, Shih-Wei Wang, Yuan-Shun Lo, Chih-Hsin Tang; Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells. Clin Sci (Lond) 1 September 2016; 130 (17): 1523–1533. doi: https://doi.org/10.1042/CS20160117
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