Tumor-associated macrophages as incessant builders and destroyers of the cancer stroma.
Tumor-associated macrophages as incessant builders and destroyers of the cancer stroma.
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DOI：
10.3390/cancers3043740
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发表时间：
2011-09-28
期刊：
影响因子：
5.2
通讯作者：
Allavena P
中科院分区：
文献类型：
--
作者：
Liguori M;Solinas G;Germano G;Mantovani A;Allavena P
肿瘤相关巨噬细胞（TAM）是肿瘤反应性基质的关键成分。在大多数（虽然不是所有）癌症中，它们的存在与患者预后不良有关。除了为肿瘤和内皮细胞释放细胞因子和生长因子外，TAM的一个显著特征是其对细胞外基质的高速降解。这种不断的基质重塑有利于基质结合生长因子的释放，并促进肿瘤细胞的运动和侵袭。此外，TAM产生基质蛋白，其中一些是典型的肿瘤组织。从人肿瘤中分离的TAM的基因表达谱揭示了基质相关的签名，编码不同基质蛋白的基因以及几种蛋白水解酶的上调。ECM组件包括：骨桥蛋白、骨激活素、胶原和纤连蛋白，还包括称为迁移刺激因子的纤连蛋白的截短同种型。除了作为结构蛋白外，这些基质组分在调节血管网络、诱导肿瘤细胞运动和降解细胞碎片中具有关键功能。蛋白水解酶包括：基质金属蛋白酶、组织蛋白酶、溶酶体和ADAM蛋白酶以及尿激酶型纤溶酶原激活物。TAM的降解活性与生物活性ECM蛋白的产生相结合，共同建立和维持最终促进肿瘤进展的炎性微环境。
Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression.