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Journal of Skin Cancer
Volume 2012 (2012), Article ID 483439, 6 pages
http://dx.doi.org/10.1155/2012/483439
Review Article

Multiple Roles for VEGF in Non-Melanoma Skin Cancer: Angiogenesis and Beyond

Department of Pathology and Integrated Biomedical Science Graduate Program, The Ohio State University, Columbus, OH 43210, USA

Received 1 September 2012; Accepted 24 September 2012

Academic Editor: Ajit K. Verma

Copyright © 2012 Kelly E. Johnson and Traci A. Wilgus. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Vascular endothelial growth factor (VEGF) is known to play a critical role in the development of non-melanoma skin cancers. VEGF is a potent pro-angiogenic factor and it is elevated in mouse and human skin tumors. The use of transgenic and knockout mice has shown that VEGF is essential for tumor development in multiple models of skin carcinogenesis and, until recently, the mechanism of action has been primarily attributed to the induction of angiogenesis. However, additional roles for VEGF have now been discovered. Keratinocytes can respond directly to VEGF, which could influence skin carcinogenesis by altering proliferation, survival, and stemness. In vivo studies have shown that loss of epidermal VEGFR-1 or neuropillin-1 inhibits carcinogenesis, indicating that VEGF can directly affect tumor cells. Additionally, VEGF has been shown to promote tumor growth by recruiting macrophages to skin tumors, which likely occurs through VEGFR-1. Overall, these new studies show that VEGF carries out functions beyond its well-established effects on angiogenesis and highlight the need to consider these alternative activities when developing new treatments for non-melanoma skin cancer.