Enhanced expression of MMP-7 and MMP-13 in inflammatory bowel disease: a precancerous potential?
Matrix metalloproteinases (MMPs) are responsible for the turnover and degradation of extracellular matrix. They play a crucial role in the growth and migration of colorectal carcinoma cells. Colorectal carcinomas are characterized by enhanced expression of MMP-2, MMP-9, MMP-7, and MMP-13. The aim of this study was to determine the expression levels of MMP-2, MMP-9, MMP-7, MMP-13, and MMP-14 and their specific inhibitor TIMP-1 in inflammatory bowel diseases and precancerous lesions of the colon, i.e., Crohn's disease and ulcerative colitis, and in adenomatous polyps (APs) for comparison. Biopsy samples of pathological and healthy tissue were obtained from 40 patients with inflammatory bowel disease (ulcerative colitis, n = 17; Crohn's disease, n = 23) and from 19 patients with APs. mRNA was measured by quantitative real-time polymerase chain reaction to study MMP and TIMP-1 gene expression in both pathological and normal mucosal specimens. For MMP-2, MMP-9, and TIMP-1, protein expression also was quantified with sandwich enzyme-linked immunosorbent assay. In biopsy specimens of Crohn's disease and ulcerative colitis, significantly increased levels of MMP-2, MMP-7, and MMP-13 mRNA were found. MMP-2 and MMP-9 showed enhanced secretion on the protein level. AP revealed an increased transcription of MMP-7 and MMP-13 genes. MMP-14 mRNA was decreased in APs. MMPs, especially MMP-7 and MMP-13, which are expressed primarily on the tumor cell surface, are elevated in inflammatory bowel disease, which may have more chance to evolve into malignancy than normal tissue. In APs, increased expression of MMP-7 and MMP-13 may serve as an early indicator for colorectal carcinogenesis.
Rath
Timo
T
Department of Internal Medicine III, University Hospital RWTH, Aachen, Germany.
Roderfeld
Martin
M
Graf
Jürgen
J
Wagner
Sandra
S
Vehr
Ann-Kathrin
AK
Dietrich
Christoph
C
Geier
Andreas
A
Roeb
Elke
E
D018256:Adenomatous Polyps / Q000201:enzymology / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000473:pathology; D003106:Colon / Q000201:enzymology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology; D003424:Crohn Disease / Q000201:enzymology / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology* / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D011480:Protease Inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7