Abstract 4276: Characterization of an ex vivo primary multicellular renal cell culture as a potential model system for renal cell carcinoma tumorigenesis

Abstract

Abstract Sporadic and germline mutations or loss of the von Hippel-Lindau (VHL) tumor suppressor gene have been linked to varying levels of risk for Renal Cell Carcinoma (RCC). RCC is a highly prevalent malignancy that affects roughly 56,000 people annually in the United States. With no true murine model for RCC, patient derived renal carcinoma cell lines and mouse embryonic stem cell lines have been largely used for the study of this malignancy. The purpose of this study is to generate an ex vivo model for Renal Cell Carcinoma using primary neonatal epithelial kidney cells grown as multicellular cultures. To better understand the genetic changes associated with RCC tumor formation following VHL loss or inactivation, primary epithelial kidney cells from newborn conditional Vhl null and Vhl G518A mutant genetically engineered mouse lines are undergoing investigation. Analysis of primary neonatal epithelial kidney cells cultured under mild hypoxia show that these cells preferentially grow in an organized multicellular spherical culture. Additionally, these multicellular cultures, termed “renospheres”, display focal expression of progenitor cell marker CD133, and also globally express Oct4 while select cells in the renospheres express renal cell type markers as seen by immunohistochemistry. Current work is aimed at identifying the cellular makeup of these spheres and determining any role individual cellular components may have in tumorigenesis. Future plans will compare growth characteristics and cellular components of renospheres in the setting of VHL mutation or loss with those with an intact VHL network. This ex vivo system can provide insight into both the cellular characteristics and molecular events that contribute substantially to RCC tumor formation as growth conditions of the renospheres are meant to mimic as close to a physiological state as possible, a factor not currently being addressed by common practices in the field. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4276. doi:10.1158/1538-7445.AM2011-4276