刘紫欣 袁宏博 陈娅斐 安海龙

摘要 生物组织中的细胞处于充满细胞外基质（ECM）的三维环境中，ECM不仅为细胞提供物理支架，还产生有关肿瘤细胞生物学功能的生化或生物物理信号。在许多模拟体内细胞—基质相互作用的方法中，利用水凝胶进行细胞培养已经揭示了一些基质机械性质协调细胞行为的基本现象。肝细胞癌（HCC）是最常见的原发性恶性肿瘤之一，其发展与组织硬度密切相关：正常的肝脏组织在受到刺激损伤后发生炎症，随后转化为肝纤维化，然后恶化为肝硬化，最终发展为肝细胞癌。随着这个过程的发展，肝组織的硬度不断增加，而增加的基质硬度又促进肝癌细胞的增殖、迁移、上皮细胞—间充质转化和耐药性，促进了HCC的发展。表明了基质机械性质在促进肝癌恶化进程中的重要作用。本文综述了细胞外基质的机械性质对肝癌发展的影响，并展望了基于力学微环境揭示肝癌病理机理的重要意义。

关 键 词 细胞外基质;肝细胞癌;硬度;水凝胶;肿瘤微环境

中图分类号 Q6     文献标志码 A

Abstract Cells are living in a three-dimensional environment filled with extracellular matrix （ECM）. ECM not only provides cells with a physical scaffold， but also generates biochemical and biophysical signals related to many biological processes. Among various approaches to mimic cell-matrix interactions in vivo， cell culture using hydrogels has revealed many basic phenomena that coordinate cell behavior. Hepatocellular carcinoma （HCC） is one of the most common primary malignancies， and its development is closely related to tissue stiffness： normal liver tissues become irritated after being stimulated and damaged， and then develop to fibrotic liver followed by cirrhosis， and transform into hepatocellular carcinoma eventually. The stiffness of liver tissues increases significantly with the development of HCC. As a reciprocity， the increased matrix stiffness further promotes the proliferation， migration， epithelial-mesenchymal transition and drug resistance of liver cancer cells. It shows that the mechanical property of matrix play an important role in HCC development. Here， we review the impact of the mechanical properties of extracellular matrix on the development of liver cancer， and  predict the significance of revealing the pathological mechanism of liver cancer based on the mechanical microenvironment.

Key words extracellular matrix; hepatocellular carcinoma; stiffness; hydrogels; tumor microenvironment

0 引言

生物组织中的细胞处于充满细胞外基质（ECM）的三维环境中，以ECM作为支架实现了细胞与细胞之间、细胞与环境之间的物质和能量交换，通过信号转导系统影响细胞的形态、代谢、功能、迁移、增殖和分化等行为。除生物化学因子外，ECM为细胞的生存和功能提供了适宜的机械力学环境，包括基底刚度、流体静压、剪切应力、应变、压力和张力等物理信号。……