The role of the VEGF-C/VEGFRs axis in tumor progression and therapy.
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.
Graduate Institute of Cancer Biology, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan. jlsu@mail.cmu.edu.tw.
Jui-Chieh
JC
Chen
Yi-Wen
YW
Chang
Chih-Chen
CC
Hong
Yang-Hao
YH
Yu
Jen-Liang
JL
Su
D000818:Animals; D018450:Disease Progression; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000628:therapy; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*
D042582:Vascular Endothelial Growth Factor C; D040262:Receptors, Vascular Endothelial Growth Factor