Opposite effects of CXCR1 and CXCR2 overexpression in prostate tumorigenesis

Abstract

Abstract Chemokines and their receptors play important role in tumor progression and metastasis. In prostate cancer (PCa), 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 tumorigenesis, using MDA PCa 2b and LNCaP cell lines. 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. CXCR1 cells showed decrease prostate specific antigen (PSA) expression whereas CXCR2 exhibited decrease androgen receptor (AR) expression. Interestingly, tumor lysates from CXCR1 cells displayed significant increase in ERK and AKT activation as well as chemokines production relative to control and CXCR2 tumors. CXCR1 tumors also exhibited a more mesenchymal phenotype, characterized by reduced E-Cadherin but increased N-Cadherin and Vimentin expression relative to CXCR2 or control tumors. Altogether, these results indicate that CXCR1 and CXCR2 may couple to distinct pathways to modulate prostate tumorigenesis. Supported by CA156735, MD012392