Abstract 3776: Bone marrow stromal cell paracrine signaling and IL-6 induce autophagy in bone metastatic prostate cancer cells

Abstract

Abstract Prostate cancer (PCa) is the second leading cause of death in North American men, where 80% of PCa mortality is due to bone metastasis. It is imperative to understand the biology of PCa cells in bone, especially as related to the role of the microenvironment in cellular adapation. Our lab recently published data revealing that bone marrow stromal cell (BMSC) paracrine signaling induces apoptosis in co-cultured bone metastatic PCa cells. However, a subpopulation of the bone metastatic PCa cells can avoid apoptotic cell death and undergo neuroendocrine differentiation (NED), a phenotype that contributes to tumor growth and is correlated with poor prognosis. One process that mediates cell survival and differentiation is autophagy, a process of sequestering cytoplasmic components for degradation and recycling to maintain cellular homeostasis. Autophagy provides a long term survival and growth advantage for cancer cells by relieving metabolic stress. Neuronal differentiation with cytoplasmic reduction is one adaptive response that can involve autophagy. Thus, we hypothesize that autophagy is a cytoprotective mechanism for PCa cell survival and NED in the bone microenvironment. To address this, we assessed the paracrine effect of BMSC on bone metastatic PCa cell autophagy and identified interleukin-6 (IL-6) as a BMSC paracrine factor that can induce PCa autophagy. We provide experimental data showing that IL-6 can protect PCa cells from apoptosis and simultaneously induce PCa NED. Current experiments are underway to determine if IL-6-induced autophagy functions upstream of bone metastatic PCa cell survival and NED and to dissect the IL-6 signaling pathway responsible for autophagy induction in PCa cells. These studies will identify IL-6 pathway components as molecular targets to attenuate cytoprotective autophagy in PCa cells in the bone microenvironment, providing new avenues for long term treatment of bone lesions in PCa patients. 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 3776. doi:10.1158/1538-7445.AM2011-3776