Cancer Division, Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.
Faculty of Medicine, St Vincent's Clinical School, UNSW Sydney, Sydney, New South Wales, Australia.
Int J Exp Pathol. 2018 Apr;99(2):58-76. doi: 10.1111/iep.12269. Epub 2018 Apr 19.
The extracellular matrix (ECM) is present in all solid tissues and considered a master regulator of cell behaviour and phenotype. The importance of maintaining the correct biochemical and biophysical properties of the ECM, and the subsequent regulation of cell and tissue homeostasis, is illustrated by the simple fact that the ECM is highly dysregulated in many different types of disease, especially cancer. The loss of tissue ECM homeostasis and integrity is seen as one of the hallmarks of cancer and typically defines transitional events in progression and metastasis. The vast majority of cancer studies place an emphasis on exploring the behaviour and intrinsic signalling pathways of tumour cells. Their goal was to identify ways to target intracellular pathways regulating cancer. Cancer progression and metastasis are powerfully influenced by the ECM and thus present a vast, unexplored repository of anticancer targets that we are only just beginning to tap into. Deconstructing the complexity of the tumour ECM landscape and identifying the interactions between the many cell types, soluble factors and extracellular-matrix proteins have proved challenging. Here, we discuss some of the emerging tools and platforms being used to catalogue and chart the ECM in cancer.
细胞外基质 (ECM) 存在于所有实体组织中,被认为是细胞行为和表型的主要调节因子。维持 ECM 的正确生化和生物物理特性以及细胞和组织动态平衡的后续调节的重要性,从一个简单的事实就可以看出,即在许多不同类型的疾病中,特别是癌症中,ECM 高度失调。组织 ECM 动态平衡和完整性的丧失被视为癌症的标志之一,通常定义了进展和转移过程中的过渡事件。绝大多数癌症研究都强调探索肿瘤细胞的行为和内在信号通路。他们的目标是确定针对调节癌症的细胞内途径的方法。癌症的进展和转移受到 ECM 的强烈影响,因此提供了一个巨大的、尚未开发的抗癌靶点库,我们才刚刚开始挖掘。剖析肿瘤 ECM 景观的复杂性,并确定许多细胞类型、可溶性因子和细胞外基质蛋白之间的相互作用,这证明是具有挑战性的。在这里,我们讨论了一些用于对癌症中的 ECM 进行编目和绘制图谱的新兴工具和平台。