Leukocytic promotion of prostate cellular proliferation

Abstract

BACKGROUND Histological evidence of pervasive inflammatory infiltrate has been noted in both benign prostatic hyperplasia/hypertrophy (BPH) and prostate cancer (PCa). Cytokines known to attract particular leukocyte subsets are secreted from prostatic stroma consequent to aging and also from malignant prostate epithelium. Therefore, we hypothesized that leukocytes associated with either acute or chronic inflammation attracted to the prostate consequent to aging or tumorigenesis may promote the abnormal cellular proliferation associated with BPH and PCa. METHODS An in vitro system designed to mimic the human prostatic microenvironment incorporating prostatic stroma (primary and immortalized prostate stromal fibroblasts), epithelium (N15C6, BPH‐1, LNCaP, and PC3 cells), and inflammatory infiltrate (HL‐60 cells, HH, and Molt‐3 T‐lymphocytes) was developed. Modified Boyden chamber assays were used to test the ability of prostate stromal and epithelial cells to attract leukocytes and to test the effect of leukocytes on prostate cellular proliferation. Antibody arrays were used to identify leukocyte‐secreted cytokines mediating prostate cellular proliferation. RESULTS Leukocytic cells migrated towards both prostate stromal and epithelial cells. CD4+ T‐lymphocytes promoted the proliferation of both transformed and non‐transformed prostate epithelial cell lines tested, whereas CD8+ T‐lymphocytes as well as dHL‐60M macrophagic and dHL‐60N neutrophilic cells selectively promoted the proliferation of PCa cells. CONCLUSIONS The results of these studies show that inflammatory cells can be attracted to the prostate tissue microenvironment and can selectively promote the proliferation of non‐transformed or transformed prostate epithelial cells, and are consistent with differential role(s) for inflammatory infiltrate in the etiologies of benign and malignant proliferative disease in the prostate. Prostate 70: 377–389, 2010.