Abstract PO-134: Differential effects of CXCR1 and CXCR2 receptors on prostate tumorigenesis

Abstract

Abstract Chemokines and their receptors are important proteins that promote growth of various malignant tumors. In prostate cancer, some members of the CXC chemokine receptor have been shown to enhance angiogenesis, proliferation and metastasis. In this study we assess the roles of the interleukin-8 (IL-8/CXCL8) receptors CXCR1 and CXCR2 in prostate cancer development, using the African American MDA PCa 2b cell line. Our results show that overexpression of CXCR2 enhanced in-vitro cell proliferation, soft agar growth and in-vivo tumor xenograft in nude mice, whereas overexpression of CXCR1 inhibited cell proliferation and tumor growth, relative to control cells. Interestingly, cells overexpressing CXCR1 exhibited a more mesenchymal phenotype, characterized by reduced E-Cadherin but increased N-Cadherin and vimentin protein expression. CXCR1 overexpression also blocked AKT activation and signal transduction. CXCR2 overexpression, however, resulted in a neuroendocrine phenotype, characterized by reduced androgen (AR) receptor expression and altered chromogranin A expression. In conclusion, these results indicate that CXCR1 and CXCR2 overexpression may play alternate roles on prostate tumorigenesis. Citation Format: Timothy O. Adekoya, Nikia Smith, Parag Kothari, Ricardo M. Richardson. Differential effects of CXCR1 and CXCR2 receptors on prostate tumorigenesis [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-134.