Abstract 6546: Iron accumulation correlates with tumor progression in mouse models of prostate cancer Free

Tumor-associated macrophages (TAMs) are well-known as anti-inflammatory immune cells that contribute to various facets of prostate cancer development. An emerging aspect of TAMs is their “iron-rich” phenotype. This accumulation of iron can contribute to cancer cell initiation and tumor progression. In the current study, we aim to explore the key role of TAMs in regulating iron balance within the prostate tumor microenvironment (TME). We induced prostate tumorigenesis in the NP mice using Tamoxifen. The NP mice (Nkx3.1^CreERT2/+ ; Pten^flox/flox ; Rosa26-CAG-LSL-EYFP/+ mice) develop prostate intraepithelial neoplasia and localized prostate adenocarcinoma by 12 months of age. We also utilized male TRAMP which spontaneously develops poorly differentiated prostate tumors reminiscent of the neuroendocrine subtype. We then stained prostate tissues using different immune cell markers and Perls''s method which stains “non-heme” iron to identify cells with high abundance of iron. Our results demonstrate that prostate tissues from two distinct transgenic prostate cancer models (adenocarcinoma and neuroendocrine), spanning different developmental stages (12 and 18 months) exhibited high level of non-heme iron in stromal regions compared with non-tumor bearing controls. The areas with high iron abundance exhibited high expression of F4/80 and the iron exporter Ferroportin-1, also known as solute carrier family 40 member 1 (SLC40A1). In summary, we found that the availability of non-heme iron correlates with the abundance of TAMs in prostate tumor microenvironment. Future studies will focus on understanding how TAMs are regulating iron availability in the dynamic tumor environment.