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肿瘤微环境对肝细胞癌进展的调控

[Control of hepatocellular carcinoma progression by the tumor microenvironment].

作者信息

Clement Bruno

机构信息

INSERM, UMR 991, Foie, Métabolismes et Cancer, CHU Pontchaillou, Université de Rennes I, 35033 Rennes.

出版信息

Bull Acad Natl Med. 2012 Jan;196(1):75-84.

Abstract

A variety of exogenous and endogenous agents, including toxic compounds, alcohol, drugs and viruses, can cause acute and chronic liver injuries which may lead to inflammation and fibrogenesis. Most hepatocellular carcinomas arise on a fibrotic or cirrhotic liver, and progression of hepatocellular carcinoma is associated with continuous changes in the cellular microenvironment. Extracellular matrix remodelling is a complex process involving synthesis and degradation of matrix components that modulate the fate of cancer cells. Proteases, including matrix metalloproteinases, cleave matrix components and release polypeptide modules with specific biological activities. Knowledge of the cellular and molecular mechanisms involved in extracellular matrix remodelling will open the path to biomarker identification and tailored treatments targeting the liver tumor microenvironment.

摘要

多种外源性和内源性因素,包括有毒化合物、酒精、药物和病毒,可导致急慢性肝损伤,进而可能引发炎症和纤维化。大多数肝细胞癌发生在纤维化或肝硬化的肝脏上,肝细胞癌的进展与细胞微环境的持续变化有关。细胞外基质重塑是一个复杂的过程,涉及基质成分的合成和降解,这些过程调节着癌细胞的命运。蛋白酶,包括基质金属蛋白酶,可切割基质成分并释放具有特定生物活性的多肽模块。了解细胞外基质重塑所涉及的细胞和分子机制将为生物标志物的识别以及针对肝肿瘤微环境的个性化治疗开辟道路。

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