Abstract 1349: Ablation of E2f3 in macrophages reduces the incidence of lung metastasis

Abstract

Abstract The tumor stroma is predominantly composed of cells of the immune system, one of them are the tumor-associated macrophages (TAMs). Tumor macrophages are recruited to the tumor in response to cytokines secreted by the tumor epithelial cells. TAMs secrete proteases into the extracellular matrix (ECM) that contributes to tumor cell intravasation. Rb-E2F axis represents one of the important pathways involved during cell cycle and is deregulated in number of cancers. E2Fs have distinct roles in the control of cell proliferation, apoptosis and differentiation pathways. We have previously shown that E2F are important downstream targets in CSF-1 signaling cascade that are involved in macrophage survival and proliferation. Present study is aimed at exploring the link between conditional ablation of E2f3 in TAM and its effect on lung metastasis using MMTV-PyMT mouse model of breast cancer. Ablation of E2f3 in the tumor macrophages resulted in a reduction of lung metastasis without affecting tumor onset or macrophage numbers. Microarray analysis of E2f3 deleted TAMs showed an up-regulation in expression of genes involved during metastasis. Our results show that E2f3 regulates the physiological processes in TAMs that inhibit lung metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1349.