title: TIMP-3 mRNA expression is regionally increased in moderately and poorly differentiated colorectal adenocarcinoma.
abstract: 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.
authors.affiliation: Department of Histopathology, Queen's Medical Centre, Nottingham, UK.
authors.forename: D G
authors.initials: DG
authors.lastname: Powe
authors.forename: J L
authors.initials: JL
authors.lastname: Brough
authors.forename: G I
authors.initials: GI
authors.lastname: Carter
authors.forename: E M
authors.initials: EM
authors.lastname: Bailey
authors.forename: W G
authors.initials: WG
authors.lastname: Stetler-Stevenson
authors.forename: D R
authors.initials: DR
authors.lastname: Turner
authors.forename: R E
authors.initials: RE
authors.lastname: Hewitt
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D015152:Blotting, Northern; D015179:Colorectal Neoplasms / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D011480:Protease Inhibitors / Q000378:metabolism*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D019717:Tissue Inhibitor of Metalloproteinase-3
chemical_list: D011480:Protease Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3