Nonapical and cytoplasmic expression of interleukin-8, CXCR1, and CXCR2 correlates with cell proliferation and microvessel density in prostate cancer.

Purpose: We characterized interleukin-8 (IL-8) and IL-8 receptor expression (CXCR1 and CXCR2) in prostate cancer to address their significance to this disease. Experimental Design: Immunohistochemistry was conducted on 40 cases of human prostate biopsy containing histologically normal and neoplastic tissue, excised frompatients with locally confined or invasive androgen-dependent prostate cancer, and 10 cases of transurethral resection of the prostatematerial frompatients with androgen-independent disease. Results:Weak to moderate IL-8 expression was strictly localized to the apical membrane of normal prostate epithelium.I n contrast, membranous expression of IL-8, CXCR1, and CXCR2 was nonapical in cancer cells of Gleason pattern 3 and 4, whereas circumferential expression was present in Gleason pattern 5 and androgen-independent prostate cancer.E ach of IL-8, CXCR1, and CXCR2were also increasingly localized to the cytoplasmof cancer cells in correlation with advancing stage of disease.Cy toplasmic expression (but not apical membrane expression) of IL-8 in Gleason pattern 3 and 4 cancer correlatedwith Ki-67 expression (R = 0. 79; P < 0.001), cyclin D1expression (R =0. 79; P < 0.001), andmicrovessel density (R =0. 81; P < 0.001). In vitro studies on androgen-independent PC3 cells confirmed the mitogenic activity of IL-8, increasing the rate of cell proliferation through activation of both CXCR1and CXCR2 receptors. Conclusions:We propose that the concurrent increase in IL-8 and IL-8 receptor expression in human prostate cancer induces autocrine signaling that may be functionally significant in initiating and promoting the progression of prostate cancer by underpinning cell proliferation and angiogenesis.