Jodele Sonata, Blavier Laurence, Yoon Janet M, DeClerck Yves A
Department of Pediatrics, USC Keck School of Medicine and the Saban Research Institute of Childrens Hospital, Los Angeles, CA 90027, USA.
Cancer Metastasis Rev. 2006 Mar;25(1):35-43. doi: 10.1007/s10555-006-7887-8.
In the 1980's, as the importance of matrix metalloproteinases (MMPs) in cancer progression was discovered, it was recognized that in most tumors these proteases were abundantly and sometimes exclusively expressed not by tumor cells, but by normal host-derived cells like fibroblasts, vascular endothelial cells, myofibroblasts, pericytes or inflammatory cells that contribute to the tumor microenvironment. Later experiments in mice deficient in specific MMPs revealed that host-derived MMPs play a critical role not only in tumor cell invasion, but also in carcinogenesis, angiogenesis, vasculogenesis and metastasis. Tumor cells secrete many factors, cytokines and chemokines that directly or indirectly increase the expression of these MMPs in the tumor microenvironment where they exert extracellular matrix (ECM) degrading and sheddase activities. The knowledge of the complex role that stromal-derived MMPs play in the interaction between tumor cells and stromal cells should allow us to consider specific windows in cancer treatment when MMP inhibition could have a valuable therapeutic effect.
20世纪80年代，随着基质金属蛋白酶（MMPs）在癌症进展中的重要性被发现，人们认识到在大多数肿瘤中，这些蛋白酶并非由肿瘤细胞大量表达，有时甚至完全不表达，而是由成纤维细胞、血管内皮细胞、肌成纤维细胞、周细胞或炎症细胞等正常宿主来源的细胞表达，这些细胞构成了肿瘤微环境。后来在缺乏特定MMPs的小鼠身上进行的实验表明，宿主来源的MMPs不仅在肿瘤细胞侵袭中起关键作用，而且在致癌作用、血管生成、血管发生和转移中也起关键作用。肿瘤细胞分泌许多因子、细胞因子和趋化因子，这些因子直接或间接增加肿瘤微环境中这些MMPs的表达，在肿瘤微环境中它们发挥细胞外基质（ECM）降解和脱落酶活性。了解基质来源的MMPs在肿瘤细胞与基质细胞相互作用中所起的复杂作用，应该能让我们在癌症治疗中考虑特定的时机，此时抑制MMPs可能会产生有价值的治疗效果。
