The epithelial-mesenchymal transition (EMT) is a transformation process mandatory for the local and distant progression of many malignant tumors, including hepatocellular carcinoma (HCC). Matrix metalloproteinases (MMPs) play significant roles in cellular regeneration, programmed death, angiogenesis, and many other essential tissular functions, involved in the normal development and also in pathological processes, such as the EMT. This paper reviews the roles of MMPs in the EMT involved in HCC invasion, as well as the ancillary roles that MMP cross-activation and tissue inhibitors play in modulating this process. While gelatinases MMP-2 and MMP-9 are the MMPs commonly cited in the EMT of HCC, MMPs belonging to other classes have been proven to be involved in this process, favoring not only invasion and metastasis (MMP-1, MMP-3, MMP-7, MMP-10, MMP-11, MMP-13, MMP-14, MMP-16, MMP-26, and MMP-28) but also angiogenesis (MMP-8 and MMP-10). There is also data suggesting that other MMPs with a suspected or demonstrated role in the EMT of other cancers may also have some degree of involvement in HCC. The auto- and cross-activation of MMPs may complicate this issue, as pinpointing the extent of implication of each MMP may be extremely difficult. The homeostasis between MMPs and their tissue inhibitors is essential in preventing tumor progression, and the disturbance of this stability is another entailed factor in the EMT of HCC, which is addressed herein.

中文翻译：

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基质金属蛋白酶在肝细胞癌上皮-间质转化中的作用

上皮-间质转化（EMT）是许多恶性肿瘤（包括肝细胞癌（HCC））的局部和远距离进展所必需的转化过程。基质金属蛋白酶（MMP）在细胞再生，程序性死亡，血管生成以及许多其他必要的组织功能中起重要作用，参与正常发育以及病理过程，例如EMT。本文综述了MMP在EMT中参与肝癌侵袭的作用，以及MMP交叉激活和组织抑制剂在调节这一过程中的辅助作用。虽然明胶酶MMP-2和MMP-9是HCC EMT中通常引用的MMP，但已证明属于其他类别的MMP参与了这一过程，不仅有利于侵袭和转移（MMP-1，MMP-3， MMP-7，MMP-10，MMP-11，MMP-13，MMP-14，MMP-16，MMP-26和MMP-28）以及血管生成（MMP-8和MMP-10）。也有数据表明，在其他癌症的EMT中具有怀疑或已证明作用的其他MMP也可能在某种程度上参与了HCC。MMP的自动激活和交叉激活可能会使这个问题复杂化，因为查明每个MMP的含义可能非常困难。MMP及其组织抑制剂之间的体内平衡对于防止肿瘤进展至关重要，而这种稳定性的紊乱是HCC EMT的另一个相关因素，在本文中对此进行了介绍。也有数据表明，在其他癌症的EMT中具有怀疑或已证明作用的其他MMP也可能在某种程度上参与了HCC。MMP的自动激活和交叉激活可能会使这个问题复杂化，因为查明每个MMP的含义可能非常困难。MMP及其组织抑制剂之间的体内平衡对于防止肿瘤进展至关重要，而这种稳定性的紊乱是HCC EMT的另一个相关因素，在本文中对此进行了介绍。也有数据表明，在其他癌症的EMT中具有怀疑或已证明作用的其他MMP也可能在某种程度上参与了HCC。MMP的自动激活和交叉激活可能会使这个问题复杂化，因为查明每个MMP的含义可能非常困难。MMP及其组织抑制剂之间的体内平衡对于防止肿瘤进展至关重要，而这种稳定性的紊乱是HCC EMT的另一个相关因素，在本文中对此进行了介绍。