Tissue levels of active matrix metalloproteinase-2 and -9 in colorectal cancer
article
The bioactivity of matrix metalloproteinases was studied in tissues from colorectal cancer patients by means of both quantitative gelatin zymography and a fluorometric activity assay. Next to paired samples of tumour tissue and distant normal mucosa (n=73), transitional tissue was analysed from a limited (n=33) number of patients. Broad-spectrum matrix metalloproteinase activity and both the active and latent forms of the gelatinases matrix metalloproteinase-2 and -9 were higher in tumour than in normal mucosa. The ratio's between active and latent forms of matrix metalloproteinase-2 and -9 were highest in tumour tissue and normal mucosa, respectively. Matrix metalloproteinase-2 levels, both active and latent forms, correlated inversely with stage of disease, the tumours without synchronous distant metastases containing significantly (P=0.005) more active matrix metalloproteinase-2 than the others. At much lower levels of activity, the same trend was observed in distant normal mucosa. The level of latent form of matrix metalloproteinase-9 in tumour depended on tumour location. Neither the active form of matrix metalloproteinase-9 nor broad-spectrum matrix metalloproteinase activity in tumour tissue did correlate with any of the clinicopathological parameters investigated. The results demonstrate explicit differences between the activity of matrix metalloproteinase-2 and -9, indicating different roles for both gelatinases in tumour progression. Such data are necessary in order to develop rational anti-cancer therapies based on inhibition of specific matrix metalloproteinases. © 2002 Cancer Research UK. Chemicals / CAS Matrix Metalloproteinase 2, EC 3.4.24.24; Matrix Metalloproteinase 9, EC 3.4.24.35; Protease Inhibitors
Topics
Colorectal cancerGelatin zymographyGelatinase activity assayMatrix metalloproteinasegelatinase Agelatinase Badultagedarticlecancer growthcancer localizationcancer stagingcolorectal cancercontrolled studycorrelation analysisenzyme activityfemalefluorometryhumanhuman tissuemajor clinical studymalemetastasispriority journaltissue levelzymographyAdenocarcinoma, MucinousAgedCell DifferentiationColonColorectal NeoplasmsFemaleHumansMaleMatrix Metalloproteinase 2Matrix Metalloproteinase 9Middle AgedNeoplasm InvasivenessNeoplasm MetastasisNeoplasm StagingProtease Inhibitors
TNO Identifier
953627
ISSN
00070920
Source
British Journal of Cancer, 86(12), pp. 1876-1883.
Pages
1876-1883
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