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.
Biological Therapies Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
N B
NB
Liabakk
I
I
Talbot
R A
RA
Smith
K
K
Wilkinson
F
F
Balkwill
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