Abstract 2536: VEGF as a potential survival factor for keratinocytes following UV exposure in vivo

• Published in: Cancer research (Chicago, Ill.) Vol. 72; no. 8_Supplement; p. 2536
• Main Authors: Nye, Kelly E., Lachey, Monica K., Parent, Allison E., Wilgus, Traci A.
• Format: Journal Article
• Language: English
• Published: 15-04-2012
• DOI: 10.1158/1538-7445.AM2012-2536
• EISSN: 1538-7445
• ISSN: 0008-5472

Non-melanoma skin cancer (NMSC) is the most prevalent type of cancer. These cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are primarily caused by chronic exposure to ultraviolet light (UV) from the sun. Vascular endothelial growth factor (VEGF) is produced by the skin in response to UV and is known to promote NMSC indirectly through the induction of angiogenesis. Evidence is emerging that VEGF can also promote skin carcinogenesis by directly affecting epidermal keratinocytes and tumor cells. In addition, epidermal keratinocytes express VEGFR-1 and proliferate and migrate directly in response to VEGF. In endothelial cells, VEGF functions as a potent survival factor by inhibiting apoptosis; however, it is not known if VEGF promotes survival in keratinocytes. Keratinocytes undergo apoptosis in response to UV exposure, a process that can be disrupted during carcinogenesis. Here, the role of VEGF and VEGFR-1 in keratinocyte and SCC-13 tumor cell survival after UV exposure was explored. Neutralizing VEGF or VEGFR-1 activity or adding VEGF did not affect UV-induced apoptosis, suggesting that VEGF-VEGFR-1 signaling is not important for keratinocyte or SCC-13 survival in vitro. The role of VEGFR-1 in keratinocyte survival was also examined in vivo. Mice with VEGFR-1-deficient keratinocytes (K14-Cre/VEGFR-1fl/fl) were generated and exposed to a single acute dose of UV light. Keratinocytes in the epidermis of K14-Cre/VEGFR-1fl/fl mice showed a significant increase in apoptosis 24 hours following UV exposure compared to K14-Cre/VEGFR-1+/+ controls. Future studies will investigate skin carcinogenesis in K14-Cre/VEGFR-1fl/fl mice chronically exposed to UV light. Overall, these results suggest that VEGFR-1 mediates the survival of keratinocytes exposed to acute UV in vivo and points to a mechanism by which VEGF could directly promote skin carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2536. doi:1538-7445.AM2012-2536