Department of Biochemical Sciences, University of Florence, Tuscany Tumor Institute and Center for Research, Transfer and High Education DenoTHE, 50134 Florence, Italy.
Cancer Lett. 2012 Nov 1;324(1):31-41. doi: 10.1016/j.canlet.2012.04.025. Epub 2012 Jun 1.
On the basis of recent advances indicating a key role of microenvironment for tumor progression, we investigated the role of fibroblasts, macrophages and hypoxia, for primary melanoma aggressiveness. Our data indicate a key role of hypoxia in stromal reactivity, acting on both myofibroblasts and machrophages differentiation. Hypoxic myofibroblasts are more active than macrophages in inducing melanoma invasiveness and exploit their oxidative stress due to hypoxia to secrete soluble factors favouring melanoma invasion and chemotaxis. We underscore the key role of microenviroment on melanoma malignancy, highlighting reactive fibroblasts, intratumoral hypoxia and oxidative stress as promising targets for melanoma antimetastatic strategies.
基于最近的研究进展表明微环境对于肿瘤进展起着关键作用，我们研究了成纤维细胞、巨噬细胞和缺氧对于原发性黑色素瘤侵袭性的作用。我们的数据表明缺氧在基质反应中起着关键作用，影响肌成纤维细胞和巨噬细胞的分化。缺氧的肌成纤维细胞比巨噬细胞更活跃，能诱导黑色素瘤的侵袭，并利用缺氧导致的氧化应激分泌有利于黑色素瘤侵袭和趋化的可溶性因子。我们强调了微环境对于黑色素瘤恶性程度的关键作用，突出了反应性成纤维细胞、肿瘤内缺氧和氧化应激作为黑色素瘤抗转移策略的有前景的靶点。
