Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10914885 | Molecular Oncology | 2014 | 18 Pages |
Abstract
We focused our interest on senescent human-derived fibroblasts in the progression of prostate cancer. Hypoxic senescent fibroblasts promote prostate cancer aggressiveness by inducing epithelial to mesenchymal transition (EMT) and by secreting energy-rich compounds to support cancer cell growth. Hypoxic senescent fibroblasts additionally increase: i) the recruitment of monocytes and their M2-macrophage polarization, ii) the recruitment of bone marrow-derived endothelial precursor cells, facilitating their vasculogenic ability and iii) capillary morphogenesis, proliferation and invasion of human mature endothelial cells. In addition, we highlight that overexpression of the hypoxia-induced miR-210 in young fibroblasts increases their senescence-associated features and converts them into cancer associated fibroblast (CAF)-like cells, able to promote cancer cells EMT, to support angiogenesis and to recruit endothelial precursor cells and monocytes/macrophages.
Keywords
M-CSFRCAFSASPSA-β-galCOXHIFhpfMmpsSISEPCHUVECSDF-1ROSsenescence-associated β-galactosidasecyclooxygenaseepithelial mesenchymal transitioninterleukinmiR-210EMTProstate cancerHuman umbilical vein endothelial cellsEndothelial progenitor cellConditioned mediumstromal cell-derived factor 1Hypoxia-inducible factorVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)Senescence-associated secretory phenotypecancer associated fibroblastTumor microenvironmentSenescenceReplicative senescenceReactive oxygen species
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Authors
Maria Letizia Taddei, Lorenzo Cavallini, Giuseppina Comito, Elisa Giannoni, Marco Folini, Alberto Marini, Paolo Gandellini, Andrea Morandi, Gianfranco Pintus, Maria Rosaria Raspollini, Nadia Zaffaroni, Paola Chiarugi,