Abstract 85: Macrophage inflammatory protein-1β and interleukin 15 modulate gene expression patterns associated with prostate cancer progression

Abstract

Abstract Prostate Cancer (PCa) is the second-leading cause of cancer-related deaths in the United States. Inflammation is associated with PCa development and progression. Cytokines such as macrophage inflammatory protein-1β (MIP1β or CCL4) and Interleukin 15 (IL-15) are differentially expressed in prostate cancer patients with recurrent disease (MIP1β) or recurrence-free survival (IL-15). However, the specific pathway by which these cytokines affect PCa progression is unknown. We evaluated the changes in gene expression patterns using in vivo models of prostate cancer and microarray analysis. To generate prostate tumors in vivo we used a mouse orthotopic xenograft model. Androgen-receptor-positive (AR+) cells, 22RV1, were orthotopically injected in the anterior prostate lobes. MIP1β and IL-15 were administered bi-weekly with intraperitoneal injections during 4 weeks. Tumor tissue was collected and snap frozen for RNA extraction, and microarray analysis with the Affymetrix Human Gene 2.0 Gene Array. Differences in gene expression were analyzed with Ingenuity Pathway Analysis (IPA) software and confirmation was done via real-time PCR. Microarray analysis showed 179 genes differentially expressed between MIP1β and control. In addition, 952 genes were differentially expressed between IL-15 and control. Ingenuity Pathway Analysis revealed that MIP1β affected networks associated with cell development, proliferation and movement while IL-15 affected networks involved in lymphocyte development and movement, cell death, and the inhibition of cancer cell invasion. Knowledge of the role of MIP1β and IL-15 in the alteration of gene expression patterns is pertinent to elucidate the significance of these cytokines in prostate cancer progression. Citation Format: Krizia Rohena-Rivera, Diana A. Aponte-Colón, María M. Sánchez-Vázquez, Carmen L. Cadilla, Magaly Martínez-Ferrer. Macrophage inflammatory protein-1β and interleukin 15 modulate gene expression patterns associated with prostate cancer progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 85.