Abstract 1510: Transcriptional profiling of a lethal breast cancer tumor microenvironment

Abstract

Abstract Breast cancer growth and progression are governed by complex and reciprocal interactions between tumor cells and surrounding stromal elements. We have previously shown that a loss of stromal Cav-1 expression is associated with an increased risk of early tumor recurrence, metastasis and decreased overall survival. To identify and characterize the signaling pathways activated in Cav-1 negative tumor stroma, we performed gene expression profiling using laser micro-dissected breast cancer associated stroma. Methods: Tumor stroma was laser capture micro-dissected using a Leica LCM system from 4 cases showing high stromal Cav-1 expression and 7 cases with loss of stromal Cav-1. Total RNA was amplified using the NuGEN™ WT-Ovation™ FFPE RNA Amplification System V2 and cDNA was hybridized to Affymetrix GeneChip® arrays. One-way ANOVA was setup to extract differentially expressed genes between Cav-1 positive and negative stromal samples. Results: We identified 238 genes that were up-regulated and 232 genes that were down-regulated in the stroma of tumors showing a loss of Cav-1 expression (p-value < = 0.01 and fold change > = 1.5) Gene set enrichment analysis revealed “stemness”, inflammation, DNA damage, oxidative stress, hypoxia, autophagy, and mitochondrial dysfunction in the tumor stroma of patients lacking stromal Cav-1. Conclusions: Our findings are consistent with the recently proposed “Autophagic Tumor Stroma Model of Cancer Metabolism”. In this model, cancer cells induce oxidative stress in adjacent stromal cells, which then forces these stromal cells to undergo autophagy. This, in turn, produces recycled nutrients to feed “hungry” cancer cells. 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 1510. doi:10.1158/1538-7445.AM2011-1510