Abstract 2032: Osteoblasts alter their protein expression profile in the presence of prostate cancer cells to facilitate their invasion

Abstract Bone metastasis is the leading cause of death in prostate cancer patients, for which there is currently no effective treatment. Since the bone microenvironment plays an important role in this process, attention has been directed to the interactions between cancer cells and the bone microenvironment, including osteoblasts. Here, we investigated the mechanism of interactions between prostate cancer cells (DU-145 and PC-3) and osteoblast cell line hFOB.1.19. We are investigating the broader effects of four different nucleoside reverse transcriptase inhibitor (NRTI) analogs 5-fluoro-1-((1R,4R)-4-hydroxycyclopent-2-en-1-yl)pyrimidine-2,4(1H,3H)-dione (KBMD-E), 3-benzoyl-5-fluoro-1-((1S,4S)-4-((tetrahydro-2H-pyran-2-yl)oxy)cyclopent-2-en-1-yl)pyrimidine-2,4(1H,3H)-dione (KBMD-G), 1-((1R,4R)-4-hydroxycyclopent-2-en-1-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (KBMD-H) and 1-(5-hydroxymethyl)-2,5-dihydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (KBMD-S) along with aPKC specific inhibitors ICA-1S and ζ-Stat to develop as potential anti-cancer drugs. Our previous publications suggested that aPKC-ι and ζ are involved in prostate cancer progression and metastasis. Current data suggested that aPKC specific inhibitors along with KBMD compounds induced apoptosis and pyroptosis of DU-145 and PC-3 while having lesser effects on hFOB.1.19 cell line. Our data demonstrate that osteoblasts assist prostate cells to establish in the bone microenvironment by producing metastatic stimulating chemokines while upregulating responsible transcription factors such as c-Jun. In addition, our preliminary data suggested that PKC-ι and ζ are crucial for driving critical steps of the metastatic cascades of prostate cancer cells. Preliminary data suggested that all 6 compounds upregulated interleukin (IL)-18 and IL-1β while downregulating IL-8, IL-6 and CXCL-1. Upregulation of Caspase 8 with cleaved gasdermin D in prostate cells indicates an increase in pyroptosis. Our preliminary results suggest that all 6 compounds can be used to disrupt the main steps of prostate cancer bone metastasis which can be targeted to develop customized, tailored therapies for bone metastatic prostate cancer which merit further research. Citation Format: Aaron J. Todman, Wishrawana S. Ratnayake, Luke Lajmi, Sloan Breedy, Abiral H. Shourav, Kirpal Bisht, Mildred Acevedo-Duncan. Osteoblasts alter their protein expression profile in the presence of prostate cancer cells to facilitate their invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2032.