Senescent stroma promotes prostate cancer progression: The role of miR-210

被引:111
作者
Taddei, Maria Letizia [1 ]
Cavallini, Lorenzo [1 ]
Comito, Giuseppina [1 ]
Giannoni, Elisa [1 ]
Folini, Marco [2 ]
Marini, Alberto [3 ]
Gandellini, Paolo [2 ]
Morandi, Andrea [1 ]
Pintus, Gianfranco [3 ]
Raspollini, Maria Rosaria [4 ]
Zaffaroni, Nadia [2 ]
Chiarugi, Paola [1 ]
机构
[1] Univ Florence, Dept Expt & Clin Biomed Sci, I-50134 Florence, Italy
[2] Fdn IRCCS Ist Nazl Turnori, Dept Expt Oncol & Mol Med, I-20133 Milan, Italy
[3] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy
[4] Univ Hosp Careggi, I-50134 Florence, Italy
关键词
Senescence; Prostate cancer; Tumor microenvironment; miR-210; CELLULAR SENESCENCE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; GENE-EXPRESSION; PREMATURE SENESCENCE; SECRETORY PHENOTYPE; TUMOR-GROWTH; HUMAN BREAST; FIBROBLASTS; PROLIFERATION;
D O I
10.1016/j.molonc.2014.07.009
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1729 / 1746
页数:18
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