Abstract 5920: Paraendocrine interactions between bone marrow mesenchymal stem cells and prostate cancer cells: impact on tumor cell invasive and proliferative capacity

Abstract

Abstract Introduction: The primary site of prostate cancer metastasis is to the bone. Bone marrow derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells resident in the bone with the potential to differentiate into osteoblasts, chondrocytes and adipocytes. They have been shown to home to sites of inflammation, including prostate cancer, contributing to tumor growth and progression. This study aims to explore the impact of metastatic prostate cancer patient derived BM-MSCs on prostate cancer cell proliferation and invasive capacity. Methodologies: BM-MSCs were isolated from bone marrow aspirates from patients diagnosed with metastatic prostate cancer (both androgen deprivation treatment naïve and commenced). Co-culture models were used to examine the impact on patient BM-MSCs versus healthy donor BM-MSCs on prostate cancer cell proliferation, PSA and cytokine secretion, and induction of cell migration and invasion. The impact of metastatic prostate cancer cells on healthy donor BM-MSCs was also examined. Results: Here we show that metastatic prostate cancer cells (PC-3 and DU145), reprogram normal donor BM-MSCs to a pro-inflammatory secretory phenotype that in turn induces prostate cancer cell invasion using a 3D spheroid model of invasion into a matrigel-collagen gel, while restricting BM-MSCs with the 3D spheroid. Additionally we isolated a series of BM-MSCs from metastatic prostate cancer patients (n=10). Results show that a proportion of prostate cancer patient derived BM-MSCs patients have a reduced differentiation capacity to osteocytes while maintaining normal adipocyte capacity. Additionally patient derived BM-MSCs increase prostate cancer cell (MDA-PCa-2b) secretion of PSA and display increased expression of inflammation associated enzymes including the immunosuppressive enzyme indoleamine- 2,3-dioxygenase and its metabolite kynurenine. Conclusions: Ultimately, we seek to decipher the role of BM-MSCs in metastatic prostate cancer, in the context of impact on androgen receptor signaling, chemotherapeutic drug response, and the maintenance and promotion of metastatic lesions. Future directions will use 3D co-culture models to identify the key regulatory networks co-activated in prostate cancer and BM-MSCs that facilitate chemotherapeutic drug resistance and metastatic progression. Note: This abstract was not presented at the meeting. Citation Format: Karen O'Leary, Sarah Ridge, William Watson, Antoinette Perry, Stephen Finn, Raymond McDermott, Sharon Anneve Glynn. Paraendocrine interactions between bone marrow mesenchymal stem cells and prostate cancer cells: impact on tumor cell invasive and proliferative capacity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5920. doi:10.1158/1538-7445.AM2017-5920