Abstract 3208: Stromal up-regulation of gene expression in prostate cancer cells: Role of microenvironment

Abstract

Abstract Recently, tumor microenvironment has been reported to be important in carcinogenesis and tumor 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 previously reported the analysis of genome-wide gene expression profiles using human PC cells (LNCaP), normal human prostate epithelial cells (PrEC), and normal human prostate stromal cells (PrSC). In that study, we identified genes that were up-regulated in LNCaP when co-cultured with PrSC, which included alpha-methylacyl-CoA racemase (AMACR), homeobox B13 (HOXB13), and UDP glucuronosyltransferase 2 family, polypeptide B17 (UGT2B17). We often confront the discrepancy in the difference of gene expression between cancer cells and tissues. Our data reveals that stromal cells could affect on PC cells to increase their gene expression, which might contribute to aggressiveness of PC cells. We then focused on secreted proteins that can mutually affect in this experimental design and identified genes that were overexpressed only in stromal cells. They included chemokine (C-C motif) ligand 2 (CCL2), hepatocyte growth factor (HGF), insulin-like growth factor binding protein 5 (IGFBP5), wingless-type MMTV integration site family, member 5A (WNT5A), and collagens (COL1A1, COL1A2, COL3A1, COL6A3, COL15A1). We further investigated the influence of these genes on the expression of AMACR, HOXB13, and UGT2B17 in PC cells to identify crucial signaling pathways in this process. This study provides potential candidate genes the products of which might serve as microenvironmental targets for the treatment of PC. Citation Format: Shingo Ashida, Chiaki Kawada, Keiji Inoue, Taro Shuin. Stromal up-regulation of gene expression in prostate cancer cells: Role of microenvironment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3208. doi:10.1158/1538-7445.AM2015-3208