Laboratory of Tumor Microenvironment, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Stezzano 87, 24126 Bergamo, Italy.
Laboratory of Tumor Microenvironment, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Stezzano 87, 24126 Bergamo, Italy.
Matrix Biol. 2023 May;119:82-100. doi: 10.1016/j.matbio.2023.03.011. Epub 2023 Mar 30.
Limited proteolysis of thrombospondins is a powerful mechanism to ensure dynamic tuning of their activities in the extracellular space. Thrombospondins are multifunctional matricellular proteins composed of multiple domains, each with a specific pattern of interactions with cell receptors, matrix components and soluble factors (growth factors, cytokines and proteases), thus with different effects on cell behavior and responses to changes in the microenvironment. Therefore, the proteolytic degradation of thrombospondins has multiple functional consequences, reflecting the local release of active fragments and isolated domains, exposure or disruption of active sequences, altered protein location, and changes in the composition and function of TSP-based pericellular interaction networks. In this review current data from the literature and databases is employed to provide an overview of cleavage of mammalian thrombospondins by different proteases. The roles of the fragments generated in specific pathological settings, with particular focus on cancer and the tumor microenvironment, are discussed.
局限性蛋白水解是确保细胞外空间中血栓素动态调节其活性的强大机制。血栓素是由多个结构域组成的多功能细胞外基质蛋白，每个结构域都与细胞受体、基质成分和可溶性因子（生长因子、细胞因子和蛋白酶）有特定的相互作用模式，因此对细胞行为和对微环境变化的反应有不同的影响。因此，血栓素的蛋白水解降解具有多种功能后果，反映了活性片段和分离结构域的局部释放、活性序列的暴露或破坏、蛋白质位置的改变以及基于 TSP 的细胞周围相互作用网络的组成和功能的变化。在这篇综述中，利用文献和数据库中的现有数据，概述了不同蛋白酶对哺乳动物血栓素的切割。讨论了在特定病理情况下生成的片段的作用，特别是在癌症和肿瘤微环境中的作用。
