4.3 Article

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

期刊

CLINICAL & EXPERIMENTAL METASTASIS
卷 31, 期 4, 页码 461-474

出版社

SPRINGER
DOI: 10.1007/s10585-014-9640-y

关键词

Prostate cancer; Brain metastasis; Astrocytes; DU145 cells; LNCaP cells; Epithelial mesenchymal transition; TGF beta

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资金

  1. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
  2. Conselho Nacional de Desenvolvimento Tecnologico (CNPq)
  3. Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)

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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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