Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancer.
Using quantitative zymography, we measured activity of the type IV collagenases metalloprotease 2 (MMP-2) and MMP-9 in 192 biopsies from colorectal carcinomas, adenomas, and normal bowel. The median level of MMP-9 in samples from Dukes' stage A (n = 18) or C (n = 48) tumors was significantly higher than in stage B carcinomas (n = 65), adenomas (n = 25), and normals (n = 36; P = 0.0001). The median level of active MMP-2 was significantly higher in stage A or C compared with adenomas (P = 0.0001) and normals (P = 0.0001). The median level of inactive MMP-2 was higher in all Dukes' stages compared with normals and adenomas (P = 0.0001). There was a significant increase in inactive MMP-2 from Jass prognostic groups I-IV (P = 0.006) but no correlation with the active enzyme. MMP activity was not related to tumor differentiation, colon versus rectal location, or disease-free, 5-year survival. All groups expressed mRNA for both enzymes, but there were quantitative and locational differences in MMP-2 mRNA expression between normal, benign, and malignant tissues. Thus MMP-2 is controlled at the level of mRNA and protein production and activation in colorectal cancer, and active MMP-2 and MMP-9 enzymes are associated strongly with Dukes' A and C stages of the disease. Variations in MMP levels with the stage or prognostic group of colorectal cancer reflect their differing stromal content.
Liabakk
N B
NB
Biological Therapies Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
Talbot
I
I
Smith
R A
RA
Wilkinson
K
K
Balkwill
F
F
D000236:Adenoma / Q000201:enzymology*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002277:Carcinoma / Q000201:enzymology*; D017364:Collagenases / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000201:enzymology*; D018093:Gelatinases / Q000096:biosynthesis*; D006801:Humans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9