Next Article in Journal
Mechanisms of Resistance to Endocrine Therapy in Breast Cancer: Focus on Signaling Pathways, miRNAs and Genetically Based Resistance
Previous Article in Journal
Spatial Regulation of Epidermal Growth Factor Receptor Signaling by Endocytosis
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
,
2
,
1
,
3 and 1,4,5,*
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 / Revised: 30 November 2012 / Accepted: 14 December 2012 / Published: 20 December 2012
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
View Full-Text   |   Download PDF [710 KB, uploaded 19 June 2014]   |   Browse Figure
SciFeed

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 VEGF-C; VEGFR-2; VEGFR-3; angiogenesis; lymphangiogenesis; metastasis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote |
RIS
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.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert