Proteolytic and non-proteolytic migration of tumour cells and leucocytes
Proteolytic and non-proteolytic migration of tumour cells and leucocytes
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DOI：
10.1042/bss0700277
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Wolf, K
中科院分区：
文献类型：
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作者：
Friedl, P;Wolf, K
不同细胞类型（如白细胞和肿瘤细胞）的迁移涉及克服三维组织网络的物理阻力的细胞策略，包括细胞外基质（ECM）组分的蛋白水解降解。高分辨率活细胞成像技术最近提供了结构和生物化学的洞察不同的使用基质降解酶的迁移过程中的不同类型的细胞在三维ECM。蛋白水解迁移是通过缓慢移动的细胞，如成纤维细胞和间质移动的肿瘤细胞，通过在细胞表面以集中的方式接合基质金属蛋白酶，组织蛋白酶和丝氨酸蛋白酶（“细胞周蛋白水解”）来实现的，而粘附和迁移牵引是由整联蛋白提供的。ECM组分的细胞周分解产生局部基质缺陷和沿沿着迁移轨道的重塑。与肿瘤细胞相反，快速移动的T淋巴细胞使用组成性非蛋白水解迁移。这种迁移类型不会产生蛋白水解基质重塑，而是依赖于形状变化，以允许细胞滑动和挤压通过结缔组织中存在的间隙和痕迹。此外，蛋白酶抑制剂可以将组成性蛋白水解迁移转化为非蛋白水解运动。在经历蛋白水解依赖性运动的肿瘤细胞中同时抑制基质金属蛋白酶、丝氨酸/苏氨酸蛋白酶和半胱氨酸蛋白酶之后，对阿米巴样运动的基本适应能够维持这些肿瘤细胞中的非蛋白水解迁移（间充质-阿米巴样转变）。肿瘤细胞不使用蛋白酶降解基质，而是使用类似白细胞的策略改变形状并沿沿着组织支架挤压基质间隙。不同细胞类型在细胞迁移中蛋白酶功能的多样性突出了药物蛋白酶抑制剂处理后细胞迁移的反应多样性和分子适应性。
The migration of different cell types, such as leucocytes and tumour cells, involves cellular strategies to overcome the physical resistance of three-dimensional tissue networks, including proteolytic degradation of extracellular matrix (ECM) components. High-resolution live-cell imaging techniques have recently provided structural and biochemical insight into the differential use of matrix-degrading enzymes in the migration processes of different cell types within the three-dimensional ECM. Proteolytic migration is achieved by slow-moving cells, such as fibroblasts and mesenchymally moving tumour cells, by engaging matrix metalloproteinases, cathepsins and serine proteases at the cell surface in a focalized manner ('pericellular proteolysis'), while adhesion and migratory traction are provided by integrins. Pericellular breakdown of ECM components generates localized matrix defects and remodelling along migration tracks. In contrast with tumour Cells, constitutive non-proteolytic migration is used by rapidly moving T lymphocytes. This migration type does not generate proteolytic matrix remodelling, but rather depends on shape change to allow cells to glide and squeeze through gaps and trails present in connective tissues. In addition, constitutive proteolytic migration can be converted into non-proteolytic movement by protease inhibitors. After the simultaneous inhibition of matrix metal loproteinases, serine/threonine proteases and cysteine proteases in tumour cells undergoing proteolysis-dependent movement, a fundamental adaptation towards amoeboid movement is able to sustain non-proteolytic migration in these tumour cells (the mesenchymal-amoeboid transition). Instead of using proteases for matrix degradation, the tumour cells use leucocyte-like strategies of shape change and squeezing through matrix gaps along tissue scaffolds. The diversity of protease function in cell migration by different cell types highlights response diversity and molecular adaptation of cell migration upon pharmacotherapeutic protease inhibitor treatment.