Khokha R, Martin D C, Fata J E
Department of Oncology, University of Western Ontario, London Regional Cancer Centre, Canada.
Cancer Metastasis Rev. 1995 Jun;14(2):97-111. doi: 10.1007/BF00665794.
The extracellular matrix (ECM) acts as both a structural scaffold and an informational medium. Its dynamic status is determined by cells that secrete its constituent molecules and, in most cases, also secrete enzymes that catalyze degradation of these molecules. A stasis between ECM degrading enzymes and their inhibitors maintains the integrity of the matrix. While controlled ECM remodelling is fundamental to several normal processes, uncontrolled disruption underlies diverse pathological conditions. Transgenic mice with specific modulations or a total lack of expression of certain metalloproteinases, serine proteinases or their inhibitors have been generated to elucidate endogenous expression patterns, identify regulatory elements of these genes, and study the physiological consequences of their deregulated expression. With these models we enhance our understanding of the role of proteinases and their inhibitors in diverse normal processes and pathologies including mammary gland development, hemostasis, emphysema and cancer.
细胞外基质（ECM）既是一种结构支架，也是一种信息介质。其动态状态由分泌其组成分子的细胞决定，并且在大多数情况下，这些细胞还分泌催化这些分子降解的酶。ECM降解酶与其抑制剂之间的平衡维持了基质的完整性。虽然受控的ECM重塑是几个正常过程的基础，但不受控制的破坏是多种病理状况的根本原因。已经产生了具有特定调节或完全缺乏某些金属蛋白酶、丝氨酸蛋白酶或其抑制剂表达的转基因小鼠，以阐明内源性表达模式、鉴定这些基因的调控元件，并研究其表达失调的生理后果。通过这些模型，我们加深了对蛋白酶及其抑制剂在包括乳腺发育、止血、肺气肿和癌症在内的多种正常过程和病理中的作用的理解。
