Urbanski S J, Edwards D R, Hershfield N, Huchcroft S A, Shaffer E, Sutherland L, Kossakowska A E
Department of Pathology, University of Calgary, Alberta, Canada.
Diagn Mol Pathol. 1993 Jun;2(2):81-9.
Several studies have implicated the extracellular matrix-degrading metalloproteinases (MMPs) as essential agents in tumor cell invasion and metastasis. In the present study, we have investigated the patterns of expression of a number of MMPs and their specific tissue inhibitors (TIMP-1 and TIMP-2) in human colonic tissue samples that represent various stages of progression from adenomas showing different degrees of dysplasia to adenocarcinomas. We assessed levels of mRNA by Northern blot analysis and the results were measured semiquantitatively by densitometry. In total, we analyzed nine adenomas of varying size and with varying degrees of dysplasia, three adenomas with adenocarcinoma (malignant polyps), and five adenocarcinomas. Although expression of MMP and TIMP mRNA was highly intercorrelated, transcripts for stromelysin 3 and TIMP-2 (high) showed the strongest relation to the neoplastic process. Detection of stromelysin 3 mRNA accompanied a diagnosis of severe dysplasia or malignancy, whereas levels of TIMP-2 (high) mRNA transcripts permitted finer distinctions on the neoplastic continuum. These data indicate changes within extracellular matrix acquired during the process of malignant transformation of human sporadic colorectal neoplasia.
多项研究表明，细胞外基质降解金属蛋白酶（MMPs）是肿瘤细胞侵袭和转移的关键因子。在本研究中，我们调查了一些MMPs及其特异性组织抑制剂（TIMP-1和TIMP-2）在人类结肠组织样本中的表达模式，这些样本代表了从显示不同程度发育异常的腺瘤到腺癌的各个进展阶段。我们通过Northern印迹分析评估mRNA水平，并通过光密度测定法进行半定量测量。我们总共分析了9个大小不同、发育异常程度不同的腺瘤，3个伴有腺癌的腺瘤（恶性息肉）和5个腺癌。虽然MMP和TIMP mRNA的表达高度相关，但基质溶解素3和TIMP-2（高）的转录本与肿瘤形成过程的关系最为密切。基质溶解素3 mRNA的检测伴随着严重发育异常或恶性肿瘤的诊断，而TIMP-2（高）mRNA转录本的水平在肿瘤连续体上允许更精细的区分。这些数据表明，在人类散发性结直肠癌的恶性转化过程中，细胞外基质发生了变化。
