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Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Clin+Cancer+Res 2015 ; 21 (5): 962-8 Nephropedia Template TP
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Molecular Pathways: Linking Tumor Microenvironment to Epithelial?Mesenchymal Transition in Metastasis #MMPMID25107915
Jung HY; Fattet L; Yang J
Clin Cancer Res 2015[Mar]; 21 (5): 962-8 PMID25107915show ga
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 TGF?, TNF? 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.