Abstract 1519: Identification and functional analysis of genes involved in cholesterol metabolism that are upregulated in prostate cancer stroma.

Abstract

Abstract Recent studies have highlighted tumor microenvironment as important in carcinogenesis and progression. Especially in prostate cancer (PC), it has been suggested that tumor microenvironment plays an important role in progression, acquisition of androgen independence, and distant metastasis. However, little is known about the genetic basis of human PC microenvironment. To clarify the mechanism of PC progression and metastasis, we investigated cross-interaction of PC epithelial cells and stromal cells by analyzing genome-wide gene expression profiles. We hypothesized that PC cells could affect on stromal cells to change their characteristics into so-called cancer-associated fibroblasts (CAFs), which might contribute to cancer invasion and metastasis. We identified genes that were up-regulated in PC stroma by analyzing gene expression profiles of normal human prostate stromal cells (PrSC) co-cultured with human PC cells (LNCaP), which included some genes involved in cholesterol metabolism, such as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). HMGCR is the rate-limiting enzyme for cholesterol synthesis and the pharmalogical target for statins. We confirmed the overexpression of HMGCR in PC stroma by immunohistochemistry. Then we knocked down endogenous HMGCR in PC cells by small interfering RNA, which resulted in the significant reduction of PC cell viability. In contrast, HMGCR overexpression stimulated PC cell growth. These results provide clues to the molecular mechanisms underlying PC invasion and metastasis, and suggest candidate genes the products of which might serve as molecular targets for the treatment of PC. Citation Format: Shingo Ashida, Chiaki Kawada, Keiji Inoue, Taro Shuin. Identification and functional analysis of genes involved in cholesterol metabolism that are upregulated in prostate cancer stroma. [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 1519. doi:10.1158/1538-7445.AM2013-1519