Abstract PO-153: ANPEP: A potential regulator of tumor-immune metabolic interactions in African American men with prostate cancer

Abstract

Abstract In prostate cancer (PCa), lack of TMPRSS2-ETS gene fusion (ETSnegative) has been a hallmark of tumor in African American (AA) as compared with European American (EA) men. To elucidate biologic features associated with ETSnegative PCa in AA men, we identified aminopeptidase N (ANPEP) as ETS-regulated gene with preferential overexpression in AA. Aminopeptidase N is involved in endocytosis, cholesterol, amino acid transport and peptide hydrolysis. In the current work, we sought to investigate the role of ANPEP in a PCa development and exploit its role in PCa metabolism as a therapeutic vulnerability, particularly in AA tumors. Methods To understand the role of ANPEP in PCa progression and therapeutic vulnerability, we determined the expression of ANPEP in different component of tumor microenvironment. We also developed a consumption and release metabolomic platform to assess the impact of ANPEP on transport of cholesterol, fatty acids and a number of relevant amino acids. Additionally, we assessed the availability of these metabolites and their end products in plasma samples of PCa patients. Results Using publicly available datasets, we showed that prostate tumors form AA men harbor the highest expression of ANPEP as compared with other groups. Using further data mining and experimental approaches, we found that aminopeptidase N is predominantly expressed on macrophages compared with prostate tumor cells, T cell, B cells, neutrophils and dendritic cells. Expression of ANPEP predominantly correlated with various amino acid transporters which also tend to be differentially expressed by ETS status. We have successfully developed a metabolomics-based approach to assess the consumption of more than 15 metabolites in prostate cancer cells and patient derived explants. Conclusion We have identified ANPEP as a macrophage-related gene with a potential role in tumor metabolism. Future work will focus on investigating functional role of ANPEP in the tumor immune microenvironment using our unique metabolic consumption/release assay in explants derived from AA and EA prostate cancer patients. Citation Format: Asmaa E. El-Kenawi, Shivanshu Awasthi, Amparo N. Serna, Jasreman Dhillon, Kosj Yamoah. ANPEP: A potential regulator of tumor-immune metabolic interactions in African American men with prostate cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-153.