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Graduate Institute of Cancer Biology, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan

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Graduate Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei 11221, Taiwan

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Department of Internal Medicine, Divisions of Pulmonary and Critical Care Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung 40447, Taiwan

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Department of Biotechnology, Asia University, No. 500, Lioufeng Road, Wufeng Shiang, Taichung 41354, Taiwan

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Center for Molecular Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung 40447, Taiwan





*

Author to whom correspondence should be addressed.



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. View Full-Text

Keywords: VEGF-C; VEGFR-2; VEGFR-3; angiogenesis; lymphangiogenesis; metastasis VEGF-C; VEGFR-2; VEGFR-3; angiogenesis; lymphangiogenesis; metastasis





Autor: Jui-Chieh Chen 1, Yi-Wen Chang 2, Chih-Chen Hong 1, Yang-Hao Yu 3 and Jen-Liang Su 1,4,5,*

Fuente: http://mdpi.com/



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