miR-205 hinders the malignant interplay between prostate cancer cells and associated fibroblasts.
Antioxid Redox Signal
; 20(7): 1045-59, 2014 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-23924028
ABSTRACT
AIMS:
Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. We have recently demonstrated that cancer-associated fibroblasts (CAFs) elicit a redox-dependent epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, driven by cycloxygenase-2/hypoxia-inducible factor-1 (HIF-1)/nuclear factor-κB pathway and enhancing tumor aggressiveness. Here, we investigated the involvement of microRNAs (miRNAs) in tumor-stroma interplay to identify possible tools to counteract oxidative stress and metastasis dissemination.RESULTS:
We found that miR-205 is the most downmodulated miRNA in PCa cells upon CAF stimulation, due to direct transcriptional repression by HIF-1, a known redox-sensitive transcription factor. Rescue experiments demonstrated that ectopic miR-205 overexpression in PCa cells counteracts CAF-induced EMT, thus impairing enhancement of cell invasion, acquisition of stem cell traits, tumorigenicity, and metastatic dissemination. In addition, miR-205 blocks tumor-driven activation of surrounding fibroblasts by reducing pro-inflammatory cytokine secretion. INNOVATION Overall, such findings suggest miR-205 as a brake against PCa metastasis by blocking both the afferent and efferent arms of the circuit between tumor cells and associated fibroblasts, thus interrupting the pro-oxidant and pro-inflammatory circuitries engaged by reactive stroma.CONCLUSION:
The evidence that miR-205 replacement in PCa cells is able not only to prevent but also to revert the oxidative/pro-inflammatory axis leading to EMT induced by CAFs sets the rationale for developing miRNA-based approaches to prevent and treat metastatic disease.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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MicroRNAs
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Fibroblastos
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Metástase Neoplásica
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article