TIMP-3 mRNA expression is regionally increased in moderately and poorly differentiated colorectal adenocarcinoma

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.