Abstract C11: The role of immune cells and androgen receptor splice variant 567 exon-skipping in prostate cancer

Abstract

Abstract Importance: Nearly all metastatic prostate cancer treated with first-line androgen deprivation therapies (ADT) will progress to castrate resistant prostate cancer (CRPC). Current ADT treatments and use are associated with upregulation of constitutively active androgen receptor splice variants. Androgen receptor splice variant 567 exon-skipping (ARv567es) is correlated with a marked decrease in 5-year survival in spite of ADT treatment. In our ARv567es mouse models, we have observed a high immune cell infiltrate in places common for mouse prostate cancer metastases such as the lung. Thus, there is an increased need to understand the role of the immune system and ARv567es in prostate cancer metastasis and resistance. Objective: To understand the role of immune cells in metastasis of prostate cancer expressing splice variants. Design: M12 human prostate cancer cells transfected with a plasmid containing ARv567es cDNA were grown in vitro and exposed to Bone Marrow Macrophages (BMM) isolated from C57BL/6 mice femurs. BMM were differentiated into M0, M1, and M2 macrophages. M1 macrophages are thought to attack tumor cells while M2 macrophages promote their growth. The following experiments were performed: proliferation studies (MTS assays), migration studies (scratch assays), and invasion studies (Boyden chambers). Results: Proliferation was significantly higher when M12 ARv567es cells were exposed to M2 conditioned medium as compared to M1 conditioned medium. Scratch assays revealed a significantly increased migration of M12 cells co-cultured with M0 and M2 conditioned medium. Boyden chamber studies demonstrated an increase in migration when M12 cells were exposed to M2 cells. Conclusions and relevance: We demonstrate in vitro evidence to support the current hypothesis of the role of the immune system in prostate cancer metastasis. Overall, our results demonstrate that immune cells, including M2 macrophages, may create a tumor microenvironment that promotes prostate cancer metastasis. Citation Format: Jared HL Hara, Stephen R. Plymate, Cynthia T. Sprenger. The role of immune cells and androgen receptor splice variant 567 exon-skipping in prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C11.