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The Role of the VEGF-C/VEGFRs Axis in Tumor Progression and Therapy
Graduate Institute of Cancer Biology, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan
Graduate Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei 11221, Taiwan
Department of Internal Medicine, Divisions of Pulmonary and Critical Care Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung 40447, Taiwan
Department of Biotechnology, Asia University, No. 500, Lioufeng Road, Wufeng Shiang, Taichung 41354, Taiwan
Center for Molecular Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung 40447, Taiwan
* Author to whom correspondence should be addressed.
Received: 26 July 2012; in revised form: 30 November 2012 / Accepted: 14 December 2012 / Published: 20 December 2012
Abstract: Vascular endothelial growth factor C (VEGF-C) has been identified as a multifaceted factor participating in the regulation of tumor angiogenesis and lymphangiogenesis. VEGF-C is not only expressed in endothelial cells, but also in tumor cells. VEGF-C signaling is important for progression of various cancer types through both VEGF receptor-2 (VEGFR-2) and VEGF receptor-3 (VEGFR-3). Likewise, both receptors are expressed mainly on endothelial cells, but also expressed in tumor cells. The dimeric VEGF-C undergoes a series of proteolytic cleavage steps that increase the protein binding affinity to VEGFR-3; however, only complete processing, removing both the N- and C-terminal propeptides, yields mature VEGF-C that can bind to VEGFR-2. The processed VEGF-C can bind and activate VEGFR-3 homodimers and VEGFR-2/VEGFR-3 heterodimers to elicit biological responses. High levels of VEGF-C expression and VEGF-C/VEGFRs signaling correlate significantly with poorer prognosis in a variety of malignancies. Therefore, the development of new drugs that selectively target the VEGF-C/VEGFRs axis seems to be an effective means to potentiate anti-tumor therapies in the future.
Keywords: VEGF-C; VEGFR-2; VEGFR-3; angiogenesis; lymphangiogenesis; metastasis
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Chen, J.-C.; Chang, Y.-W.; Hong, C.-C.; Yu, Y.-H.; Su, J.-L. The Role of the VEGF-C/VEGFRs Axis in Tumor Progression and Therapy. Int. J. Mol. Sci. 2013, 14, 88-107.
Chen J-C, Chang Y-W, Hong C-C, Yu Y-H, Su J-L. The Role of the VEGF-C/VEGFRs Axis in Tumor Progression and Therapy. International Journal of Molecular Sciences. 2013; 14(1):88-107.
Chen, Jui-Chieh; Chang, Yi-Wen; Hong, Chih-Chen; Yu, Yang-Hao; Su, Jen-Liang. 2013. "The Role of the VEGF-C/VEGFRs Axis in Tumor Progression and Therapy." Int. J. Mol. Sci. 14, no. 1: 88-107.