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.
KeywordsProstate cancer Brain metastasis Astrocytes DU145 cells LNCaP cells Epithelial mesenchymal transition TGFβ
Epithelial mesenchymal transition
Transforming growth factor beta
Central nervous system
Fetal bovine serum
Conditioned medium collected after 24 h of culture
Conditioned medium collected after 48 h of culture
Phosphate buffered saline
Glial fibrillary acidic protein
The authors thank Dr. Vivaldo Moura Neto for discussion and comments on the study; Dr. Jane Faria and Morgana Ferreira Sobrinho for the encouragement; and Maria Aparecida de Oliveira Domingos and Grasiella Ventura for technical assistance. This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Tecnológico (CNPq), and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ).
Conflict of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
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