Abstract 1541: M2 macrophages co-cultured with prostate cancer cells promote osteoblast differentiation mediated by BMP-2 and BMP-7.

Abstract

Abstract Prostate cancers frequently metastasize to bone and cause predominantly osteoblastic lesions. When tumor cells metastasize to bone, they interact with the bone microenvironment. Bidirectional interactions between prostate cancer cells and bone microenvironment increase expression of cytokines, chemokines and adhesion molecules. These factors can be produced by tumor cells as well as bone marrow cells including osteoclasts, osteoblasts/stromal cells and macrophages. It has been demonstrated that M2 macropahge enhanced tumor growth, survival and metastasis. However, whether M2 macropahges play roles in prostate cancer-induced osteoblastic lesions, specifically in osteoblast differentiation is unknown. We initially isolated M2 macrophages from primary murine bone marrow cells culturing with IL-4 and IL-13. Then M2 macrophages were co-cultured with or without prostate cancer C4-2B or LNCaP cells at ratio 5:1. Then the conditioned media (CM) from M2 co-cultures were collected. We incubated murine bone marrow cells or MC3T3 E1 cells with different concentrations of the CM and performed Von Kossa Staining. We found that the co-cultured CM, but not the CM collected from either macrophages or prostate cancer cells, significantly induced bone marrow cells or MC3T3 E1 mineralization in vitro. This induction was partially blocked by anti-BMP-2 and anti-BMP-7 neutralizing antibodies. We further observed that the co-cultured CM significantly induced alkaline phosphatase (ALP) and osteocalcin (OCN) production. Finally, we determined the cytokine productions from the co-cultured CM by using ELISA. The production of BMP-2 and BMP-7 were detected. The conditioned media collected from M1 macrophage were used as corresponding and negative controls throughout the whole study. We concluded that M2 macrophages co-cultured with prostate cancer cells promote osteoblast differentiation mediated by BMP-2 and BMP-7. Supported by NSF projects 81171993 and 81272415; NSF key project 81130046; 973 Grant (2009CB918902); Guangxi projects 201201ZD004 and 2012GXNSFCB53004. Citation Format: Lihui Wang, Xin Huang, Jianhua Wang, Yi Lu. M2 macrophages co-cultured with prostate cancer cells promote osteoblast differentiation mediated by BMP-2 and BMP-7. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1541. doi:10.1158/1538-7445.AM2013-1541