Abstract 4923: Identification of invasive and metastatic potential of Tpl2 knockout keratinocytes.

Abstract

Abstract Skin cancer is the most common form of cancer in the United States, with an estimated two million cases diagnosed annually. Tpl2 (MAP3K8) is a serine threonine protein kinase in the mitogen-activated protein kinase (MAPK) signal transduction cascade. Tpl2 was identified by our laboratory as having a tumor suppressive function in skin carcinogenesis. Tpl-2 knockout mice develop significantly more tumors than matched wildtype controls and have a larger degree of inflammation when challenged with 12-O-tetradecanoylphorbol-13-acetate (TPA). However, it is unknown whether the tumors that develop in Tpl2 knockout mice are more aggressive and invasive than skin tumors in wildtype mice. Therefore, we compared the invasive and metastatic potential of keratinocytes from wildtype and Tpl2 knockout mice. Using various techniques including gene microarray, real-time polymerase chain reaction, and zymography we found MMP-2 and MMP-9 matrix metalloproteinases to be significantly up-regulated in Tpl-2−/- keratinocytes. Additionally, Tpl-2−/- keratinocytes have altered migration rates, significantly higher malignant conversion rates and increased angiogenesis when compared to wildtype keratinocytes. Moreover, protein arrays identified several angiogenic factors, in addition to the MMP's, induced in Tpl-2−/- keratinocytes. In summary, our studies demonstrate skin tumors from Tpl-2−/- mice have the potential to be more aggressive, invasive, and metastatic than tumors in control animals. Citation Format: Katie L. Decicco-Skinner, Sarah Jung, Tracy Tabib, Curtis Gwilliam, Hepzi Alexander, Sarah Goodheart, Adam Morin, Alex Cvitan, Jonathan Wiest. Identification of invasive and metastatic potential of Tpl2 knockout keratinocytes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4923. doi:10.1158/1538-7445.AM2013-4923