Malignant invasion of the central nervous system: the hidden face of a poorly understood outcome of prostate cancer.

Malignancies of the central nervous system include primary brain tumors and brain metastases, the latter being the major cause of intracranial neoplasms in adults. Although prostate cancer (PCa) brain metastases are not the most common source, recent data show that the relevance of prostate cancer brain metastases (PCBM) cannot be neglected. In this review, we focus on the molecular repertory as well as on the phenotypical similarities between PCBM and primary PCa, such as the cellular evolution and the maintenance of androgen-receptor expression. Moreover, the simultaneous occurrence of PCBM with other PCa metastatic sites and the significance of the clinical heterogeneity of the disease are also discussed. In addition, a potential relationship between the heterogeneous behavior exhibited by PCBM and the co-occurrence of malignant cell clusters with distinct genetic profiles is also hypothesized, as well as the prominent role of astrocytes in the establishment of PCBM.

The reciprocal interactions between astrocytes and prostate cancer cells represent an early event associated with brain metastasis.

Tumor establishment, growth, and survival are supported by interactions with microenvironment components. Here, we investigated whether the interactions between prostate cancer cells and cortical astrocytes are associated to a potential role for astrocytes in tumor establishment. We demonstrate that astrocytes interact in vitro with prostatic cancers cells derived from different metastatic sites. Astrocytes and their secreted extracellular matrix, stimulate DU145 cell (a brain-derived prostate tumor cell line) proliferation while inhibiting cell death and modulating the expression of several genes related to prostate cancer progression, suggesting the activation of EMT process in these cells. In contrast, DU145 cells and their conditioned medium inhibited cell proliferation and induced cell death of astrocytes. On the other hand, the astrocytes were unable to significantly induce an increment of LNCaP cell (a lymph node-derived prostate tumor cell line) proliferative activity. In addition, LNCaP cells were also unable to induce cell death of astrocytes. Thus, we believe that DU145 cells, but not LNCaP cells, present an even more aggressive behavior when interacting with astrocytes. These results provide an important contribution to the elucidation of the cellular mechanisms involved in the brain microenvironment colonization.