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

International Journal of Molecular Sciences

Jui-Chieh Chen¹  Yi-Wen Chang²  Chih-Chen Hong¹  Yang-Hao Yu³ 

[1] Graduate Institute of Cancer Biology, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan; E-Mails:;Graduate Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei 11221, Taiwan; E-Mail:;Department of Internal Medicine, Divisions of Pulmonary and Critical Care Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung 40447, Taiwan

关键词: VEGF-C;    VEGFR-2;    VEGFR-3;    angiogenesis;    lymphangiogenesis;    metastasis;   

DOI  :  10.3390/ijms14010088

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.