RESUMO
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.
Assuntos
Adenocarcinoma/secundário , Neoplasias Encefálicas/secundário , Neoplasias da Próstata/patologia , Adenocarcinoma/genética , Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias da Próstata/genética , Receptores Androgênicos/genéticaRESUMO
Cancer has been mainly treated by traditional therapeutic approaches which do not consider the human genetic diversity and present limitations, probably as a consequence of a poor knowledge of both patient's genetic background and tumor biology. Due to genome project conclusion and large-scale gene analyses emergence, the therapeutic management of several prevalent and aggressive tumors has dramatically improved and represents the closest examples of a precision medicine intervention in this field. Nonetheless, prostate cancer (PCa) remains as a challenge to personalized medicine implementation, probably due to its notorious heterogeneous molecular profile. Cancer treatment personalized approaches rely on the premise that a well-defined panorama of tumor molecular alterations can help selecting new and specific therapeutic targets for its treatment and potentially discriminate tumors which behave differentially. Lately, molecular and genetic studies have been investigating PCa basis, revealing multiple recurrent genomic alterations that include mutations, DNA copy-number variations, rearrangements, and gene fusions, among others. In addition to the increment on PCa molecular biology knowledge, mapping the molecular alterations pattern of this neoplasia, especially the differences existent between tumors displaying distinct behaviors, could represent a great improvement concerning the identification of new targets, personalized medicine, and patients' management and prognosis.
Assuntos
Medicina de Precisão/métodos , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Terapia de Alvo Molecular , Prognóstico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/terapiaRESUMO
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.