The origin of prostate metastases: emerging insights

The outcome of patients with prostate cancer (PCa) is mainly dependent on the presence or absence of distant metastases. Although several advances have been made in understanding the biological basis of this tumor, the mechanisms underlying PCa metastatic spread are not fully clear. The lack of a clear origin for PCa metastasis may be partially due to the evidence of PCa heterogeneity between primary tumor and metastases and among different metastatic sites. Cross-metastatic seeding and the de novo monoclonal seeding of daughter metastases have been proposed as crucial events during metastasis. This process requires the contribution of tumor environment, which modulates cancer cell homing and growth, and involves several components including cancer stem cells (CSCs), tumor secreted microvesicles, circulating tumor cells (CTCs), and immune cells. In this review, we have focused on the recent findings on the origin of prostate metastasis, showing the contribution of tumor microenvironment to this evolutionary process.