Int. J. Mol. Sci. 2013, 14(1), 88-107; doi:10.3390/ijms14010088
Review

The Role of the VEGF-C/VEGFRs Axis in Tumor Progression and Therapy

1 Graduate Institute of Cancer Biology, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan 2 Graduate Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei 11221, Taiwan 3 Department of Internal Medicine, Divisions of Pulmonary and Critical Care Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung 40447, Taiwan 4 Department of Biotechnology, Asia University, No. 500, Lioufeng Road, Wufeng Shiang, Taichung 41354, Taiwan 5 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
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.

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