Tumor-associated stromal cells as key contributors to the tumor microenvironment.
Tumor-associated stromal cells as key contributors to the tumor microenvironment.
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DOI：
10.1186/s13058-016-0740-2
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发表时间：
2016-08-11
期刊：
影响因子：
--
通讯作者：
Marini FC
中科院分区：
文献类型：
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作者：
Bussard KM;Mutkus L;Stumpf K;Gomez-Manzano C;Marini FC
肿瘤微环境是由肿瘤块和支持细胞组成的异质细胞群。越来越明显的是，这些支持细胞被癌细胞从附近的内源性宿主基质募集，并促进诸如肿瘤血管生成、增殖、侵袭和转移的事件，以及介导治疗抗性的机制。此外，募集的基质细胞类型多样，包括血管内皮细胞、周细胞、脂肪细胞、成纤维细胞和骨髓间充质基质细胞。在正常伤口愈合和炎症过程中，局部基质细胞改变其表型，成为反应性基质。然而，在某些条件下，肿瘤细胞可以吸收这些反应性基质细胞，并进一步将其转化为肿瘤相关基质细胞（TASC）。这些TASC表达更高水平的蛋白质，包括α-平滑肌肌动蛋白，成纤维细胞活化蛋白和基质金属蛋白酶，与它们的正常，非反应性对应物相比。还已知TASC分泌许多促肿瘤发生因子，包括IL-6、IL-8、基质衍生因子-1 α、血管内皮生长因子、生腱蛋白-C和基质金属蛋白酶等，其将额外的肿瘤和促肿瘤发生细胞募集到发育中的微环境中。在这里，我们回顾了目前的文献有关的起源招募宿主间质，对肿瘤进展的贡献，肿瘤相关的基质细胞，内源性宿主间质和肿瘤细胞之间的串扰机制。
The tumor microenvironment is a heterogeneous population of cells consisting of the tumor bulk plus supporting cells. It is becoming increasingly evident that these supporting cells are recruited by cancer cells from nearby endogenous host stroma and promote events such as tumor angiogenesis, proliferation, invasion, and metastasis, as well as mediate mechanisms of therapeutic resistance. In addition, recruited stromal cells range in type and include vascular endothelial cells, pericytes, adipocytes, fibroblasts, and bone-marrow mesenchymal stromal cells. During normal wound healing and inflammatory processes, local stromal cells change their phenotype to become that of reactive stroma. Under certain conditions, however, tumor cells can co-opt these reactive stromal cells and further transition them into tumor-associated stromal cells (TASCs). These TASCs express higher levels of proteins, including alpha-smooth muscle actin, fibroblast activating protein, and matrix metalloproteinases, compared with their normal, non-reactive counterparts. TASCs are also known to secrete many pro-tumorigenic factors, including IL-6, IL-8, stromal-derived factor-1 alpha, vascular endothelial growth factor, tenascin-C, and matrix metalloproteinases, among others, which recruit additional tumor and pro-tumorigenic cells to the developing microenvironment. Here, we review the current literature pertaining to the origins of recruited host stroma, contributions toward tumor progression, tumor-associated stromal cells, and mechanisms of crosstalk between endogenous host stroma and tumor cells.