TIMP-3 mRNA expression is regionally increased in moderately and poorly differentiated colorectal adenocarcinoma
TIMP-3 mRNA expression is regionally increased in moderately and poorly differentiated colorectal adenocarcinoma
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DOI：
10.1038/bjc.1997.285
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发表时间：
1997-06-01
影响因子：
8.8
通讯作者：
Hewitt, RE
中科院分区：
文献类型：
--
作者：
Powe, DG;Brough, JL;Hewitt, RE
在这项研究中，我们报告的组织抑制剂基质金属蛋白酶-3（TIMP-3）mRNA的表达在人类正常大肠粘膜，腺瘤和腺癌的分布。北方印迹分析显示，5 TIMP-3 mRNA转录本存在于正常粘膜上皮和中，低分化癌。腺瘤和高分化癌在本部分研究中未进行检查。原位杂交结果显示正常组织和腺瘤组织中均未检测到TIMP-3 mRNA。相反，TIMP-3 mRNA定位于结直肠癌中的基质成纤维细胞样细胞，与高分化癌相比，中分化组和低分化组的发病率增加。在中度和低分化肿瘤组的表达是最强的肿瘤浸润边缘，没有低分化癌显示mRNA表达的区域提前的浸润边缘，相比之下，3的12个中度组。据我们所知，这是第一个详细的报告TIMP-3 mRNA在结直肠肿瘤的区域定位。我们认为，缺乏TIMP-3 mRNA表达的宿主间质组织中的低分化癌可能有助于其增加的侵袭性。
In this study, we report on the distribution of tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) mRNA expression in human normal colorectal mucosa, adenomas and adenocarcinomas. Northern blot analysis showed five TIMP-3 mRNA transcripts to be present in normal mucosal epithelium and in moderately and poorly differentiated carcinoma. Adenomas and well-differentiated carcinomas were not examined in this part of the investigation. In situ hybridization studies showed no detectable TIMP-3 mRNA in normal and adenomatous tissue. In contrast, TIMP-3 mRNA is localized to stromal fibroblast-like cells in colorectal carcinomas, with an increased incidence in moderately and poorly differentiated groups compared with well-differentiated carcinomas. Expression in both the moderately and the poorly differentiated tumour groups was strongest at the tumour invasive edge; none of the poorly differentiated carcinomas showed mRNA expression in regions ahead of the invasive edge, compared with 3 of 12 of the moderate group. To our knowledge, this is the first detailed report on the regional localization of TIMP-3 mRNA in colorectal tumours. We suggest that the lack of TIMP-3 mRNA expression in host stromal tissues ahead of poorly differentiated carcinomas may contribute to their increased invasiveness.