Abstract 4282: Analysis of epithelial and stromal cell networks in prostate cancer by gene expression profiles

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. The prognosis of PC is related to invasion and metastasis. Epithelial-to-mesenchymal transition (EMT) has gained considerable attention as a conceptual paradigm to explain invasive and metastatic behavior during cancer progression. EMT is a normal physiologic process by which cells of epithelial origin convert into cells with mesenchymal characteristics. It has been proposed that EMT is induced by cancer cells during metastatic dissemination from a primary organ to secondary sites, but how EMT occurs during PC invasion and metastasis remains uncertain. 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. Likewise, CAFs could affect on surrounding normal epithelial cells to change their characteristics into PC cells. We first analyzed three of genome-wide gene expression profiles; normal human prostate stromal cells (PrSC) co-cultured with human prostate cancer cells (LNCaP), LNCaP co-cultured with PrSC, and human prostate epithelial cells (PrEC) co-cultured with cancer-associated PrSC which is PrSC previously co-cultured with LNCaP. Before microarray analysis, we confirmed the overexpression of alpha-smooth muscle actin in PrSC co-cultured with LNCaP, which means the transition from normal stromal cells to CAFs. We then analyzed networks among PC cells, stromal cells, and surrounding normal epithelial cells by analyzing gene expression profiles and validated our data using real-time PCR, immunohistochemistry, and bioinformatics. These data 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: {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 4282. doi:1538-7445.AM2012-4282