Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer.
Colorectal cancer is one of the commonest malignant tumors and has a relatively poor prognosis. The outcome depends on the extent of local and particularly metastatic tumor spread. The matrix metalloproteinases (MMPs) are a family of closely related enzymes that degrade the extracellular matrix and are considered to be important in facilitating tumor invasion and spread (1-3). Using immunohistochemistry we have investigated the occurrence in colorectal cancer of MMP-1 (interstitial collagenase). Our monoclonal antibody was prepared against a synthetic peptide corresponding to an amino acid sequence specific for MMP-1 and was selected to react in formalin-fixed wax-embedded sections, thus allowing use in diagnostic histopathology and also enabling access to archival material. We found that the presence of MMP-1 in colorectal cancer is associated with a poor prognosis (P = 0.006) and has prognostic value independent of Dukes stage. One MMP inhibitor that strongly inhibits MMP-1 has already been shown to inhibit growth of human colon cancer xenografts in nude mice (4). Our results suggest that treatment of those individuals whose colon tumors produce MMP-1 with MMP inhibitors is a therapeutic strategy worth pursuing.
Murray
G I
GI
Department of Pathology, University of Aberdeen, Aberdeen, UK.
Duncan
M E
ME
O'Neil
P
P
Melvin
W T
WT
Fothergill
J E
JE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis*; D017364:Collagenases / Q000032:analysis* / Q000276:immunology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D020781:Matrix Metalloproteinase 1; D051379:Mice; D011379:Prognosis; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D017364:Collagenases; D020781:Matrix Metalloproteinase 1