Division of Biomedical Sciences, St George's Medical School, University of London, Cranmer Terrace, London, UK.
J Endocrinol. 2011 May;209(2):139-51. doi: 10.1530/JOE-10-0377. Epub 2011 Feb 9.
Extracellular matrices (ECM) are secreted molecules that constitute the cell microenvironment, composed of a dynamic and complex array of glycoproteins, collagens, glycosaminoglycans and proteoglycans. ECM provides the bulk, shape and strength of many tissues in vivo, such as basement membrane, bone and cartilage. In vitro, most animal cells can only grow when they are attached to surfaces through ECM. ECM is also the substrate for cell migration. However, ECM provides much more than just mechanical and structural support, with implications in developmental patterning, stem cell niches and cancer. ECM imparts spatial context for signalling events by various cell surface growth factor receptors and adhesion molecules such as integrins. The external physical properties of ECM may also have a role in the signalling process. ECM molecules can be flexible and extendable, and mechanical tension can expose cryptic sites, which could further interact with growth factors or their receptors. ECM proteins and structures can determine the cell behaviour, polarity, migration, differentiation, proliferation and survival by communicating with the intracellular cytoskeleton and transmission of growth factor signals. Integrins and proteoglycans are the major ECM adhesion receptors which cooperate in signalling events, determining the signalling outcomes, and thus the cell fate. This review focuses on the emerging concept of spatial cell biology of ECM, especially the current understanding of integrins and heparan sulphate proteoglycans as the essential cellular machineries that sense, integrate and respond to the physical and chemical environmental information either by directly connecting with the local adhesion sites or by regulating global cellular processes through growth factor receptor signalling pathways, leading to the integration of both external and internal signals in space and time.
细胞外基质 (ECM) 是分泌的分子，构成细胞微环境，由动态和复杂的糖蛋白、胶原蛋白、糖胺聚糖和蛋白聚糖组成。ECM 为体内许多组织提供了大部分的形状、强度和体积，如基底膜、骨骼和软骨。在体外，大多数动物细胞只有在通过 ECM 附着在表面上时才能生长。ECM 也是细胞迁移的基质。然而，ECM 提供的不仅仅是机械和结构支持，它还与发育模式、干细胞龛和癌症有关。ECM 通过各种细胞表面生长因子受体和粘附分子（如整联蛋白）为信号事件提供空间背景。细胞外基质的外部物理特性也可能在信号过程中发挥作用。ECM 分子可以是灵活和可伸展的，机械张力可以暴露隐藏的结合位点，这些结合位点可以进一步与生长因子或其受体相互作用。ECM 蛋白和结构可以通过与细胞内细胞骨架的通讯和生长因子信号的传递来决定细胞的行为、极性、迁移、分化、增殖和存活。本文综述了 ECM 空间细胞生物学的新观点，特别是对整合素和硫酸乙酰肝素蛋白聚糖作为基本细胞机制的当前理解，这些机制可以通过直接连接局部粘附位点或通过调节全球细胞过程来感知、整合和响应物理和化学环境信息生长因子受体信号通路，从而在空间和时间上整合外部和内部信号。
