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转化生长因子-β促进活肝癌中上皮间质转化的形态力学效应。

Transforming Growth Factor-β Promotes Morphomechanical Effects Involved in Epithelial to Mesenchymal Transition in Living Hepatocellular Carcinoma.

机构信息

Department of the Medical Sciences and Human Oncology, University Aldo Moro, 70124 Bari, Italy.

CNR Nanotec-Institute of Nanotechnology, 73100 Lecce, Italy.

出版信息

Int J Mol Sci. 2018 Dec 28;20(1):108. doi: 10.3390/ijms20010108.

DOI:10.3390/ijms20010108
PMID:30597907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6337381/
Abstract

The epithelial mesenchymal transition (EMT) is a physiological multistep process involving epithelial cells acquiring a mesenchymal-like phenotype. It is widely demonstrated that EMT is linked to tumor progression and metastasis. The transforming growth factor (TGF)-β pathways have been widely investigated, but its role in the hepatocarcinoma EMT is still unclear. While the biochemical pathways have been extensively studied, the alteration of biomechanical behavior correlated to cellular phenotype and motility is not yet fully understood. To better define the involvement of TGF-β1 in the metastatic progression process in different hepatocarcinoma cell lines (HepG2, PLC/PRF/5, HLE), we applied a systematic morphomechanical approach in order to investigate the physical and the structural characteristics. In addition, we evaluated the antitumor effect of LY2157299, a TGF-βR1 kinase inhibitor, from a biomechanical point of view, using Atomic Force and Confocal Microscopy. Our approach allows for validation of biological data, therefore it may be used in the future as a diagnostic tool to be combined with conventional biomolecular techniques.

摘要

上皮间质转化（EMT）是一个涉及上皮细胞获得间充质样表型的生理多步骤过程。广泛证明 EMT 与肿瘤进展和转移有关。转化生长因子（TGF）-β途径已被广泛研究，但它在肝癌 EMT 中的作用仍不清楚。虽然生物化学途径已被广泛研究，但与细胞表型和运动相关的生物力学行为的改变尚不完全清楚。为了更好地定义 TGF-β1 在不同肝癌细胞系（HepG2、PLC/PRF/5、HLE）中的转移进展过程中的作用，我们应用了系统的形态力学方法来研究物理和结构特征。此外，我们还从生物力学的角度评估了 TGF-βR1 激酶抑制剂 LY2157299 的抗肿瘤作用，使用原子力和共聚焦显微镜。我们的方法允许对生物学数据进行验证，因此它可能在未来被用作与常规生物分子技术相结合的诊断工具。

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