Abstract 1489: The role of bone marrow adipocyte-induced HO-1 expression in prostate tumor survival in bone

Abstract

Abstract Prostate cancer (PCa) is the second leading cause of cancer deaths among men in the United States. Obesity, adipocyte-derived signals, and adipose tissue inflammation are major contributors to development of aggressive PCa, with higher recurrence and higher mortality rates. Bone is a primary site of metastasis of PCa and obese and overweight men have a three-fold higher risk of progression to metastatic disease compared to normal-weight men receiving the same treatment. Experimental and clinical evidence indicate that bone marrow adipocyte numbers increase with age and obesity and their increased presence affects homeostasis in the bone microenvironment. It is not, however, currently known how adipocyte-derived factors influence tumor growth and survival in bone. Heme oxygenase 1 (HO-1) is a stress-responsive protein induced by hypoxia and inflammation, and it has been shown to play a role in prostate carcinogenesis and cell survival. Its role in tumor cell aggressiveness and survival in response to adipocyte-derived signals has not been previously explored. Here, we investigated the effects of bone marrow adipocyte-derived factors on HO-1/IL-1α pathway in PCa cells. Our study was driven by hypothesis that adipocytes increase invasiveness and survival of PCa cells via upregulation of HO-1. We utilized Taqman RT PCR analyses and western blotting approaches to demonstrate that levels of HO-1 and its inducer IL-1α increase in PC3, DU145 and C42B prostate cancer cell lines in response to treatment with adipocyte conditioned media (Adipo CM). Immunofluorescence analyses and subcellular fractionation methods were used to demonstrate a translocation of HO-1 from the cytoplasm to nucleus upon exposure to Adipo CM. Invasiveness of PCa cells in response to adipocyte-derived factors in the absence and presence of IL-1α neutralizing antibody and HO-1 inhibitor Zinc protoporphyrin IX was assessed using Boyden chamber assays. Studies are currently underway to determine the significance of HO-1/IL-1α upregulation in tumor cells survival and response to chemotherapy. Collectively, the results of our studies demonstrate that adipocyte-induced upregulation of HO-1/IL-1α pathways may be playing a significant role in promoting prostate tumor aggressiveness and survival. 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 1489. doi:1538-7445.AM2012-1489