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Journal of Translational Medicine

, 11:164

Cancer microenvironment


BackgroundThe epithelial-to-mesenchymal transition EMT and mesenchymal-to-epithelial transition MET play pivotal roles in metastasis of epithelial cancers. The distinction between them has shed new light on the molecular mechanisms of tumor metastasis. Recently, tumor microenvironment TM has been identified as one of the most potent inducers of EMT and MET. TM is characterized by its complexity and flexibility. The purpose of this study was to ascertain the exact effect of each distinct TM component on the evolution hepatocellular carcinoma HCC metastasis.

MethodsTwo different cell culture models were used. The HCC cell line Bel-7402 was co-cultured with the normal liver cell line HL-7702 or with the retinal vascular endothelial cell line RF-6A in double-layer six-well plates, imitating the direct interaction between tumor-host cells and tumor cells. Bel-7402 was also cultured in the conditioned medium CM of the human lung fibroblast cell line MRC-5, HL-7702 or RF-6A, imitating an indirect interaction. Integrin β1, β3, β4, β7, laminin β3, E-cadherin and Snail levels were measured by quantitative RT-PCR in tumor sepecimens from 42 resected HCC.

ResultsWe found that Bel-7402 cells co-cultured with HL-7702 or RF-6A cells were induced to undergo MET. The expression of E-cadherin, α-catenin and β-catenin was up-regulated, accompanied with a strengthened E-cadherin-catenin complex on the membrane of co-cultured Bel-7402 cells. Consequently, the invasion and migration ability of cells was declined. Conversely, Bel-7402 cells cultured in conditioned medium from MRC-5 cells underwent an EMT-like transformation as the cells became elongated with increased invasion and migration ability. Furthermore, we demonstrated that HL-7702 cells could generally inhibit the tumorigenicity and viability of Bel-7402 cells. We also found that integrin β1 expression was negatively associated with capsular formation, and that integrin β4 expression was negatively associated with CK19 expression.

ConclusionOur findings highlight the strong influences exerted by TM on tumor progression through EMT and MET by impacting the expression of adhesion molecules, including the E-cadherin-catenin complex, laminins and integrins.

KeywordsTumor microenvironment EMT MET Co-culture Conditioned medium culture Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-11-164 contains supplementary material, which is available to authorized users.

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Autor: Songming Ding - Wu Zhang - Zhiyuan Xu - Chunyang Xing - Haiyang Xie - Haijun Guo - Kanjie Chen - Penghong Song - Yu Gu -


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