Murray G I, Duncan M E, O'Neil P, McKay J A, Melvin W T, Fothergill J E
Department of Pathology, University of Aberdeen, U.K.
J Pathol. 1998 Jul;185(3):256-61. doi: 10.1002/(SICI)1096-9896(199807)185:3<256::AID-PATH115>3.0.CO;2-A.
The matrix metalloproteinases (MMPs) are a family of closely related proteolytic enzymes which are involved in the degradation of different components of the extracellular matrix. There is increasing evidence to indicate that individual MMPs have an important role in tumour invasion and tumour spread. Monoclonal antibodies specific for MMP-1, MMP-2, or MMP-9 have been produced, using as immunogens peptides selected from the amino acid sequences of individual MMPs. The presence of MMP-1, MMP-2, and MMP-9 in oesophageal cancer was investigated by immunohistochemistry on formalin-fixed, wax-embedded sections of oesophageal cancers. The relationship of individual MMPs to prognosis and survival was determined. MMP-1 was present in 24 per cent of oesophageal cancers, while MMP-2 and MMP-9 were present in 78 and 70 per cent of tumours, respectively. The presence of MMP-1 was associated with a particularly poor prognosis (log rank test 8.46, P < 0.004) and was an independent prognostic factor (P = 0.02). The identification of individual MMPs in oesophageal cancer provides a rational basis for use in the treatment of oesophageal cancer of MMP inhibitors which are currently undergoing clinical trial.
基质金属蛋白酶(MMPs)是一族密切相关的蛋白水解酶,参与细胞外基质不同成分的降解。越来越多的证据表明,单个MMP在肿瘤侵袭和肿瘤扩散中起重要作用。已制备出针对MMP-1、MMP-2或MMP-9的单克隆抗体,所用免疫原是从单个MMP的氨基酸序列中选取的肽段。通过对福尔马林固定、石蜡包埋的食管癌切片进行免疫组织化学,研究了MMP-1、MMP-2和MMP-9在食管癌中的存在情况。确定了单个MMP与预后和生存的关系。24%的食管癌中存在MMP-1,而MMP-2和MMP-9分别存在于78%和70%的肿瘤中。MMP-1的存在与特别差的预后相关(对数秩检验8.46,P<0.004),并且是一个独立的预后因素(P = 0.02)。在食管癌中鉴定单个MMP为目前正在进行临床试验的MMP抑制剂用于食管癌治疗提供了合理依据。