期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 14, 期 12, 页码 2361-2371出版社
MARY ANN LIEBERT INC
DOI: 10.1089/ars.2010.3727
关键词
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资金
- Associazione Italiana Ricerca sul Cancro (AIRC), Istituto Toscano Tumori
- Fondazione Cassa di Risparmio di Lucca
Cancer-associated fibroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial mesenchymal transition (EMT) of tumor cells and their achievement of stem cell traits. We demonstrate that CAFs induce EMT and stemness through a proinflammatory signature, which exploits reactive oxygen species to drive a migratory and aggressive phenotype of prostate carcinoma cells. CAFs exert their propelling role for EMT in strict dependence on cycloxygenase-2 (COX-2), nuclear factor-kappa B, and hypoxia-inducible factor-1. CAF-secreted metalloproteases elicit in carcinoma cells a Rac1b/COX-2-mediated release of reactive oxygen species, which is mandatory for EMT, stemness, and dissemination of metastatic cells. Tumor growth is abolished, and metastasis formation is severely impaired by RNA interfering-mediated targeting of the proinflammatory signature, thereby supporting the therapeutic targeting of the circuitry COX-2/nuclear factor-kappa B /hypoxia-inducible factor-1 as a valuable antimetastatic tool affecting cancer cell malignancy. Antioxid. Redox Signal. 14, 2361-2371.
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