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Abstract 3392: Molecular determinants for the bone-metastatic potential of prostate cancer cells
Journal article   Peer reviewed

Abstract 3392: Molecular determinants for the bone-metastatic potential of prostate cancer cells

Qingxin Liu, Danielle Jernigan and Alessandro Fatatis
Cancer research (Chicago, Ill.), v 72(8_Supplement), pp 3392-3392
15 Apr 2012
DOI: https://doi.org/10.1158/1538-7445.AM2012-3392

Abstract

Abstract Skeletal metastasis is the major cause of morbidity and death in patients with advanced prostate cancer (PCa). The propensity of cancer cells to progress into macroscopic lesions at secondary sites relies on the successful adaptation of Disseminated Tumor Cells (DTCs) to the new microenvironment. This requirement explains the predilection of most tumors to produce clinical metastases in selected organs although they can seed malignant cells also in several other tissues. It seems plausible that the metastatic fate of DTCs is dictated by the pleiotropic effects of specific genes and their encoded products establishing functional interactions with the surrounding stroma. The main objective of this study was to identify these molecular mediators of cell survival and growth in the bone with the ultimate goal of identifying effective therapeutic targets to counteract PCa metastases. Using a pre-clinical animal model of experimental metastasis, we have recently shown that exogenous over-expression of PDGFRα in non-metastatic prostate phenotypes conferred bone-metastatic potential and a monoclonal antibody targeting the receptor reduced bone metastatic tumors by more than 70%. Here we report that comparative gene-expression analyses conducted with PCa cells showing different intrinsic metastatic potential, as well as prostate phenotypes that fail to increase their metastatic behavior upon PDGFRα expression, resulted in a bone-metastatic gene signature including three genes encoding for soluble, secreted proteins. This suggests that DTCs with aggressive metastatic behavior modify the bone microenvironment in their favor, not only coercing the stroma to support their own survival, but also allowing other malignant phenotypes, that would otherwise fail to thrive, to grow into macroscopic tumors. We are currently testing this cell-cooperation in metastasis as well as functionally validating our three-gene signature by stably silencing or over-expressing each of the three newly identified genes in bone-metastatic and non-metastatic PCa cells, respectively. 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 3392. doi:1538-7445.AM2012-3392

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