Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
Mol Oncol. 2014 Dec;8(8):1729-46. doi: 10.1016/j.molonc.2014.07.009. Epub 2014 Jul 21.
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.
我们关注的是衰老的人源性成纤维细胞在前列腺癌进展中的作用。缺氧衰老的成纤维细胞通过诱导上皮间质转化(EMT)和分泌能量丰富的化合物来支持癌细胞生长,从而促进前列腺癌的侵袭性。缺氧衰老的成纤维细胞还增加了:i)单核细胞的募集及其 M2 巨噬细胞极化,ii)骨髓源性内皮前体细胞的募集,促进其血管生成能力,iii)人成熟内皮细胞的毛细血管形态发生、增殖和侵袭。此外,我们强调,在年轻成纤维细胞中过表达缺氧诱导的 miR-210 会增加其衰老相关特征,并将其转化为癌相关成纤维细胞(CAF)样细胞,能够促进癌细胞 EMT、支持血管生成,并募集内皮前体细胞和单核细胞/巨噬细胞。