The reciprocal interactions between astrocytes and prostate cancer cells represent an early event associated with brain metastasis |
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Authors: | Eliane Gouvêa de Oliveira Barros Antonio Palumbo Jr. Pedro Lucas Prado Mello Rômulo Medina de Mattos Julianna Henriques da Silva Bruno Pontes Nathan Bessa Viana Rackele Ferreira do Amaral Flavia Regina Souza Lima Nathalia Meireles da Costa Celia Yelimar Palmero Leandro Miranda-Alves Christina Maeda Takiya Luiz Eurico Nasciutti |
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Affiliation: | 1. Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 2. LPO/COPEA, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 3. Instituto de Física, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 4. Programa de Carcinogênese Molecular, Centro de Pesquisas (CPQ), Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil 5. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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Abstract: | 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. |
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