Radiation Oncology Branch, Center for Cancer Research, NCI/NIH, Advanced Technology Center, 8717 Grovemont Circle, Bethesda, MD 20892-4605, USA.
Semin Cancer Biol. 2010 Jun;20(3):161-8. doi: 10.1016/j.semcancer.2010.05.002. Epub 2010 May 12.
Cells adhere to one another and/or to matrices that surround them. Regulation of cell-cell (intercellular) and cell-matrix adhesion is tightly controlled in normal cells, however, defects in cell adhesion are common in the majority of human cancers. Multilateral communication among tumor cells with the extracellular matrix (ECM) and neighbor cells is accomplished through adhesion molecules, ECM components, proteolytic enzymes and their endogenous inhibitors. There is sufficient evidence to suggest that reduced adherence is a tumor cell property engaged during tumor progression. Tumor cells acquire the ability to change shape, detach and easily move through spaces disorganizing the normal tissue architecture. This property is due to changes in expression levels of adhesion molecules and/or due to elevated levels of secreted proteolytic enzymes, including matrix metalloproteinases (MMPs). Among other roles, MMPs degrade the ECM and, therefore, prepare the path for tumor cells to migrate, invade and spread to distant secondary areas, where they form metastasis. Tissue inhibitors of metalloproteinases or TIMPs control MMP activities and, therefore, minimize matrix degradation. Both MMPs and TIMPs are involved in tissue remodeling and decisively regulate tumor cell progression including tumor angiogenesis. In this review, we describe and discuss data that support the important role of MMPs and TIMPs in cancer cell adhesion and tumor progression.
细胞彼此黏附,或黏附于周围的基质。在正常细胞中,细胞-细胞(细胞间)和细胞-基质黏附的调控非常严格,然而,细胞黏附的缺陷在大多数人类癌症中很常见。肿瘤细胞与细胞外基质(ECM)和相邻细胞之间的多向通讯是通过黏附分子、ECM 成分、蛋白水解酶及其内源性抑制剂来实现的。有充分的证据表明,黏附能力下降是肿瘤细胞在肿瘤进展过程中所具有的特性。肿瘤细胞获得了改变形状、脱离并轻易地穿过空间的能力,从而破坏了正常的组织结构。这种特性归因于黏附分子表达水平的变化,或归因于分泌型蛋白水解酶(包括基质金属蛋白酶(MMPs))水平的升高。除了其他作用外,MMPs 降解 ECM,因此为肿瘤细胞迁移、侵袭和扩散到远处的继发区域,从而形成转移开辟了道路。金属蛋白酶组织抑制剂或 TIMPs 控制 MMP 的活性,从而最小化基质降解。MMPs 和 TIMPs 都参与组织重塑,并在包括肿瘤血管生成在内的肿瘤细胞进展中起决定性作用。在这篇综述中,我们描述并讨论了支持 MMPs 和 TIMPs 在肿瘤细胞黏附和肿瘤进展中重要作用的数据。