Molecular pathways: linking tumor microenvironment to epithelial-mesenchymal transition in metastasis.
Molecular pathways: linking tumor microenvironment to epithelial-mesenchymal transition in metastasis.
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DOI：
10.1158/1078-0432.ccr-13-3173
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发表时间：
2015-03-01
期刊：
影响因子：
--
通讯作者：
Yang J
中科院分区：
文献类型：
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作者：
Jung HY;Fattet L;Yang J
在肿瘤发展过程中，肿瘤细胞通过生物化学和生物物理线索与周围的微环境不断交流。特别是，肿瘤微环境可以指导癌细胞经历称为上皮-间充质转化（EMT）的形态发生程序，以促进局部侵袭和转移性传播。越来越多的证据揭示了促进EMT的大量微环境因素，包括局部活化的基质细胞分泌的促炎细胞因子、缺氧条件、细胞外基质成分和机械性质。在这里，我们回顾了肿瘤微环境中直接影响EMT计划的各种生化和生物物理因素。具体地说，细胞因子如TGFβ、TNFα和IL 6以及缺氧能够在各种肿瘤中诱导EMT。几种细胞外基质（ECM）蛋白，包括胶原蛋白-I、纤连蛋白和Hybryonan，以及通过细胞外赖氨酰氧化酶的ECM重塑也涉及调节EMT。在临床前研究和正在进行的临床试验中，靶向这些肿瘤微环境信号已显示出阻止各种人类癌症肿瘤进展的前景。
During tumor development, tumor cells constantly communicate with the surrounding microenvironment through both biochemical and biophysical cues. In particular, the tumor microenvironment can instruct carcinoma cells to undergo a morphogenesis program termed epithelial-to-mesenchymal transition (EMT) to facilitate local invasion and metastatic dissemination. Growing evidence uncovered a plethora of microenvironmental factors in promoting EMT, including pro-inflammatory cytokines secreted by locally activated stromal cells, hypoxia conditions, extracellular matrix components, and mechanical properties. Here, we review various biochemical and biophysical factors in the tumor microenvironment that directly impinge upon the EMT program. Specifically, cytokines such as TGFβ, TNFα and IL6 and hypoxia are capable of inducing EMT in various tumors. Several extracellular matrix (ECM) proteins, including Collagen-I, Fibronectin, and Hyaluronan, and ECM remodeling via extracellular Lysyl oxidase are also implicated in regulating EMT. In preclinical studies and ongoing clinical trials, targeting these tumor microenvironmental signals has shown promises in halting tumor progression in various human cancers.