Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; Divison of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
Breast. 2013 Aug;22 Suppl 2:S66-72. doi: 10.1016/j.breast.2013.07.012.
The extracellular matrix (ECM) is composed of highly variable and dynamic components that regulate cell behavior. The protein composition and physical properties of the ECM govern cell fate through biochemical and biomechanical mechanisms. This requires a carefully orchestrated and thorough regulation considering that a disturbed ECM can have serious consequences and lead to pathological conditions like cancer. In breast cancer, many ECM proteins are significantly deregulated and specific matrix components promote tumor progression and metastatic spread. Intriguingly, several ECM proteins that are associated with breast cancer development, overlap substantially with a group of ECM proteins induced during the state of tissue remodeling such as mammary gland involution. Fibrillar collagens, fibronectin, hyaluronan and matricellular proteins are matrix components that are common to both involution and cancer. Moreover, some of these proteins have in recent years been identified as important constituents of metastatic niches in breast cancer. In addition, specific ECM molecules, their receptors or enzymatic modifiers are significantly involved in resistance to therapeutic intervention. Further analysis of these ECM proteins and the downstream ECM mediated signaling pathways may provide a range of possibilities to identify druggable targets against advanced breast cancer.
细胞外基质（ECM）由高度可变和动态的成分组成，这些成分调节细胞行为。ECM 的蛋白质组成和物理特性通过生化和生物力学机制控制细胞命运。这需要精心协调和彻底的调控，因为 ECM 的紊乱可能会产生严重的后果，并导致癌症等病理状况。在乳腺癌中，许多 ECM 蛋白显著失调，特定的基质成分促进肿瘤进展和转移扩散。有趣的是，一些与乳腺癌发展相关的 ECM 蛋白与组织重塑过程中诱导的一组 ECM 蛋白（如乳腺退化）有很大的重叠。纤维胶原、纤维连接蛋白、透明质酸和基质细胞蛋白是退化和癌症共有的基质成分。此外，近年来，这些蛋白质中的一些已被确定为乳腺癌转移灶的重要组成部分。此外，特定的 ECM 分子、它们的受体或酶修饰物显著参与了对治疗干预的耐药性。对这些 ECM 蛋白及其下游 ECM 介导的信号通路的进一步分析可能为确定针对晚期乳腺癌的可用药靶提供一系列可能性。
