Oral Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

The influence of macrophages on prostate cancer progression (#163)

Nils Nesheim 1 , Stuart Ellem 1 , Gail Risbridger 1
  1. Monash University, Clayton, VICTORIA, Australia

Prostate cancer (PCa) is the most common cancer among men and still the fourth leading cause of mortality among Australian males. The mechanism of carcinogenesis remains poorly understood, but current research highlights the importance of inflammatory signaling in the tumor microenvironment. In particular, the presence of mast cells and tumor-associated macrophages (TAM) at the tumor site has been linked to poor survival rates in many cancers, pointing out a pivotal role of these cell types in cancer. Previous studies from our working group could show that cancer associated fibroblasts (CAF) from patient radical prostatectomy specimen were able to induce morphological changes in benign prostate epithelial cells (BPH‑1) that are associated with a cancerous phenotype. Introduction of mast cells into the system was capable to further enhance this change of BPH-1 cell shape. In a similar fashion, this study investigates the role of in-vitro polarized macrophages on the tumor microenvironment. After polarization of the stable THP-1 cell line, generated M1 or M2 (TAM-like) subtype macrophages will be co-cultured with prostatic fibroblasts and BPH-1 cells in a 2.5D co-culture system to give insights on how macrophages drive tumor progression. To further show if tumor-derived factors have the ability to skew macrophage maturation, THP-1 cells will be polarized in the presence of conditioned media (CM) of patient‑derived CAF/NPF. Initial data suggests that CAF/NPF CM leads to differential regulation of macrophage-specific transcripts and that macrophages lead to destabilization of the BPH-1 cell interaction with the extracellular matrix. These preliminary results help explain the detrimental effect of intratumoral macrophages on patient survival.