Munshi H G, Stack M S
Division of Hematology/Oncology; Department of Medicine; Robert H. Lurie Comprehensive Cancer Center, Jesse Brown VA Medical Center, Northwestern University Feinberg Medical School, Chicago, IL 60611, USA.
Cancer Metastasis Rev. 2006 Mar;25(1):45-56. doi: 10.1007/s10555-006-7888-7.
A predominant characteristic of metastatic cells is the ability to invade host tissues and establish distant metastatic foci. Release of metastatic cells from a primary tumor results from disruption of tissue architecture and requires reversible modulation of cell-matrix and cell-cell contacts, cytoskeletal rearrangement, and acquisition of enhanced proteolytic potential. Malignant cells produce a spectrum of extracellular proteinases including matrix metalloproteinases (MMPs) that process extracellular matrix components, cell surface proteins, and immune modulators. Dysregulated proteolysis has been implicated in tumor invasion and metastasis in multiple model systems. This review will focus on data that highlight the influence of cell-matrix and cell-cell interactions and their associated signal transduction pathways on proteinase regulation. These data highlight cell adhesion signaling as a mechanism for a versatile cellular proteolytic response to changing microenvironmental cues.
转移细胞的一个主要特征是能够侵入宿主组织并形成远处转移灶。原发肿瘤中转移细胞的释放源于组织结构的破坏，需要细胞与基质以及细胞与细胞之间接触的可逆调节、细胞骨架重排，并获得增强的蛋白水解潜能。恶性细胞会产生一系列细胞外蛋白酶，包括处理细胞外基质成分、细胞表面蛋白和免疫调节剂的基质金属蛋白酶（MMPs）。蛋白水解失调在多个模型系统中都与肿瘤侵袭和转移有关。本综述将聚焦于突出细胞与基质以及细胞与细胞相互作用及其相关信号转导途径对蛋白酶调节影响的数据。这些数据突出了细胞黏附信号传导作为细胞对不断变化的微环境线索做出多功能细胞蛋白水解反应的一种机制。
