Behrens Peter, Mathiak Micaela, Mangold Elisabeth, Kirdorf Simona, Wellmann Axel, Fogt Franz, Rothe Marcus, Florin Alexandra, Wernert Nicolas
Institute of Pathology, University of Bonn, Bonn, Germany.
Int J Cancer. 2003 Nov 1;107(2):183-8. doi: 10.1002/ijc.11336.
Hereditary nonpolyposis colorectal cancers (HNPCCs) are an important subgroup of colorectal carcinomas. Compared to sporadic variants, they present several particular features, the most important of which are less invasive and metastatic properties linked to a more favorable prognosis. This contrasts to the generally poor differentiation of the epithelial tumor component. Since matrix-degrading proteases secreted by stromal fibroblasts contribute significantly to tumor invasion, we analyzed the stromal expression of 2 matrix metalloproteinases (MMP-1 and -9) and of one of their regulators, the Ets 1 transcription factor, by both immunohistochemistry and in situ hybridization in sporadic colorectal carcinomas and HNPCC tumors. We found that MMP-1 and -9 as well as Ets 1 are upregulated in the fibroblastic stroma during the development from sporadic adenomas to invasive carcinomas. HNPCC tumors exhibited a significantly lower expression of Ets 1, MMP-1 and -9. These findings on the basis of lower matrix-degrading properties of the fibroblastic tumor stroma in HNPCC tumors might help to explain why, in spite of their less differentiated phenotype, HNPCC tumors have a less invasive and metastatic potential compared to sporadic cancers.
遗传性非息肉病性结直肠癌（HNPCC）是结直肠癌的一个重要亚组。与散发性变体相比，它们具有几个特殊特征，其中最重要的是侵袭性和转移性较低，预后更有利。这与上皮肿瘤成分通常分化较差形成对比。由于基质成纤维细胞分泌的基质降解蛋白酶对肿瘤侵袭有显著贡献，我们通过免疫组织化学和原位杂交分析了散发性结直肠癌和HNPCC肿瘤中两种基质金属蛋白酶（MMP-1和-9）及其调节因子之一Ets 1转录因子的基质表达。我们发现，从散发性腺瘤发展到浸润性癌的过程中，MMP-1和-9以及Ets 1在成纤维细胞基质中上调。HNPCC肿瘤中Ets 1、MMP-1和-9的表达显著降低。基于HNPCC肿瘤中成纤维细胞肿瘤基质较低的基质降解特性的这些发现，可能有助于解释为什么尽管HNPCC肿瘤的表型分化较差，但与散发性癌症相比，其侵袭和转移潜力较小。
