Enhanced expression of MMP-7 and MMP-13 in inflammatory bowel disease: A precancerous potential?
Enhanced expression of MMP-7 and MMP-13 in inflammatory bowel disease: A precancerous potential?
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DOI：
10.1097/01.mib.0000234133.97594.04
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发表时间：
2006-11-01
影响因子：
4.9
通讯作者：
Roeb, Elke
中科院分区：
文献类型：
--
作者：
Rath, Timo;Roderfeld, Martin;Roeb, Elke
基质金属蛋白酶（Matrix metalloproteinases，MMPs）是细胞外基质的代谢和降解酶。它们在结直肠癌细胞的生长和迁移中起着至关重要的作用。结直肠癌的特征在于MMP-2、MMP-9、MMP-7和MMP-13的表达增强。本研究的目的是确定MMP-2、MMP-9、MMP-7、MMP-13和MMP-14及其特异性抑制剂TIMP-1在炎症性肠病和结肠癌前病变中的表达水平，即，克罗恩病和溃疡性结肠炎，并在腺瘤性息肉（AP）中进行比较。从40例炎症性肠病患者（溃疡性结肠炎，n = 17;克罗恩病，n = 23）和19例AP患者中获得病理组织和健康组织的活检样本。采用实时定量聚合酶链反应检测MMP和TIMP-1基因在病理组织和正常黏膜组织中的表达。对于MMP-2、MMP-9和TIMP-1，蛋白表达也用夹心酶联免疫吸附测定法定量。在克罗恩病和溃疡性结肠炎的活检标本中，MMP-2、MMP-7和MMP-13的mRNA水平显著升高，MMP-2和MMP-9在蛋白水平上分泌增强。AP显示MMP-7和MMP-13基因转录增加。AP中MMP-14 mRNA表达减少。MMP，尤其是MMP-7和MMP-13，主要表达于肿瘤细胞表面，在炎性肠病中升高，其可能比正常组织更有机会演变成恶性肿瘤。在AP中，MMP-7和MMP-13的表达增加可作为结直肠癌发生的早期指标。
Matrix metalloproteinases (MMPs) are responsible for the turnover and degradation of extracellular matrix. They play a crucial role in the growth and migration of colorectal carcinoma cells. Colorectal carcinomas are characterized by enhanced expression of MMP-2, MMP-9, MMP-7, and MMP-13. The aim of this study was to determine the expression levels of MMP-2, MMP-9, MMP-7, MMP-13, and MMP-14 and their specific inhibitor TIMP-1 in inflammatory bowel diseases and precancerous lesions of the colon, i.e., Crohn's disease and ulcerative colitis, and in adenomatous polyps (APs) for comparison. Biopsy samples of pathological and healthy tissue were obtained from 40 patients with inflammatory bowel disease (ulcerative colitis, n = 17; Crohn's disease, n = 23) and from 19 patients with APs. mRNA was measured by quantitative real-time polymerase chain reaction to study MMP and TIMP-1 gene expression in both pathological and normal mucosal specimens. For MMP-2, MMP-9, and TIMP-1, protein expression also was quantified with sandwich enzyme-linked immunosorbent assay. In biopsy specimens of Crohn's disease and ulcerative colitis, significantly increased levels of MMP-2, MMP-7, and MMP-13 mRNA were found. MMP-2 and MMP-9 showed enhanced secretion on the protein level. AP revealed an increased transcription of MMP-7 and MMP-13 genes. MMP-14 mRNA was decreased in APs. MMPs, especially MMP-7 and MMP-13, which are expressed primarily on the tumor cell surface, are elevated in inflammatory bowel disease, which may have more chance to evolve into malignancy than normal tissue. In APs, increased expression of MMP-7 and MMP-13 may serve as an early indicator for colorectal carcinogenesis.