Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou 730000, PR China.
Orthopaedics Key Laboratory of Gansu Province, Lanzhou 730000, PR China.
Biomed Pharmacother. 2021 Sep;141:111899. doi: 10.1016/j.biopha.2021.111899. Epub 2021 Jul 30.
The microenvironment surrounding the tumor affects biological processes, such as cell proliferation, angiogenesis, apoptosis, and invasion. Therefore, the ability to change these environments is an important attribute for tumor cells to obtain specific functions necessary for growth and metastasis. Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic metalloenzymes that facilitate protease-dependent tumor progression by degrading extracellular matrix (ECM) proteins, releasing cytokines, growth factors, and other cell surface molecules. As one of the most widely studied MMPs, MMP-11 is an important protease that is expressed in cancer cells, stromal cells, and the adjacent microenvironment. MMP-11 has a dual effect on tumors. On one hand, MMP-11 promotes tumor development by inhibiting apoptosis and promoting the migration and invasion of cancer cells in the early stage. On the other hand, in animal models, MMP-11 has a protective effect on tumor growth and metastasis at an advanced stage. Based on current findings regarding the importance of MMP-11 in altering the tumor microenvironment, there is a need to further understand how stromal cells and the ECM regulate tumor progression, which may result in the re-examination of MMPs as drug targets for cancer and other diseases. In this review, we summarize the dual role of MMP-11 in cancer and its potential clinical significance.
肿瘤周围的微环境会影响生物学过程,如细胞增殖、血管生成、细胞凋亡和侵袭。因此,改变这些环境的能力是肿瘤细胞获得生长和转移所需特定功能的重要属性。基质金属蛋白酶(MMPs)是锌依赖性蛋白水解金属酶,通过降解细胞外基质(ECM)蛋白、释放细胞因子、生长因子和其他细胞表面分子,促进蛋白酶依赖性肿瘤进展。作为研究最广泛的 MMPs 之一,MMP-11 是一种在癌细胞、基质细胞和相邻微环境中表达的重要蛋白酶。MMP-11 对肿瘤具有双重作用。一方面,MMP-11 通过抑制细胞凋亡和促进癌细胞在早期的迁移和侵袭来促进肿瘤的发展。另一方面,在动物模型中,MMP-11 在晚期对肿瘤生长和转移具有保护作用。基于目前关于 MMP-11 改变肿瘤微环境的重要性的发现,有必要进一步了解基质细胞和 ECM 如何调节肿瘤进展,这可能会重新审视 MMPs 作为癌症和其他疾病的药物靶点。在这篇综述中,我们总结了 MMP-11 在癌症中的双重作用及其潜在的临床意义。
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