Androgen receptor negatively influences the expression of chemokine receptors (CXCR4, CCR1) and ligand-mediated migration in prostate cancer DU-145

Abstract

We previously reported that androgen receptor (AR) plays a role in the regulation of adhesion to the extracellular matrix and invasion of human prostate cancer cells by influencing the expression of specific integrin subunits. It is now considered that chemokines play a significant role in organ-selective cancer metastasis. In this study, we hypothesized that AR may influence the expression of these chemokine receptors and cell function. The mRNA expression of chemokine receptors in human prostate cancer cell line DU-145 and DU-145 cells expressing AR (DU-145/AR) was investigated by RT-PCR. DU-145 cells selectively expressed CXCR4 and CCR1 mRNA at high levels compared with DU-145/AR cells. DU-145 showed vigorous migratory responses to its ligand CXCL12 (also called stromal-derived factor-1alpha, SDF-1alpha) and CCL3 (also called macrophage inflammatory protein-1, MIP-1alpha). In contrast, neither CXCL12 nor CCL3 affected the migration of DU-145/AR cells. These results indicate that expression of AR down-regulates the migratory responses of human prostate cancer cells via chemokine and its receptor systems.