Ghajar Cyrus M, Bissell Mina J
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-8206, USA.
Histochem Cell Biol. 2008 Dec;130(6):1105-18. doi: 10.1007/s00418-008-0537-1. Epub 2008 Nov 14.
The extracellular matrix (ECM), once thought to solely provide physical support to a tissue, is a key component of a cell's microenvironment responsible for directing cell fate and maintaining tissue specificity. It stands to reason, then, that changes in the ECM itself or in how signals from the ECM are presented to or interpreted by cells can disrupt tissue organization; the latter is a necessary step for malignant progression. In this review, we elaborate on this concept using the mammary gland as an example. We describe how the ECM directs mammary gland formation and function, and discuss how a cell's inability to interpret these signals -- whether as a result of genetic insults or physicochemical alterations in the ECM -- disorganizes the gland and promotes malignancy. By restoring context and forcing cells to properly interpret these native signals, aberrant behavior can be quelled and organization re-established. Traditional imaging approaches have been a key complement to the standard biochemical, molecular, and cell biology approaches used in these studies. Utilizing imaging modalities with enhanced spatial resolution in live tissues may uncover additional means by which the ECM regulates tissue structure, on different length scales, through its pericellular organization (short-scale) and by biasing morphogenic and morphostatic gradients (long-scale).
细胞外基质（ECM）曾被认为仅仅为组织提供物理支撑，而现在被视为细胞微环境的关键组成部分，负责引导细胞命运并维持组织特异性。那么，可以合理推断，ECM自身的变化或者ECM信号传递给细胞或被细胞解读的方式发生改变，都可能破坏组织的组织结构；而后者是恶性进展的必要步骤。在本综述中，我们以乳腺为例详细阐述这一概念。我们描述了ECM如何引导乳腺的形成和功能，并讨论了细胞由于基因损伤或ECM的物理化学改变而无法解读这些信号时，是如何使腺体紊乱并促进恶性肿瘤发展的。通过恢复环境并促使细胞正确解读这些天然信号，可以抑制异常行为并重新建立组织结构。传统成像方法一直是这些研究中使用的标准生化、分子和细胞生物学方法的关键补充。在活组织中利用具有更高空间分辨率的成像方式，可能会揭示ECM通过其细胞周围组织（短尺度）以及通过影响形态发生和形态稳定梯度（长尺度）在不同长度尺度上调节组织结构的其他方式。
