Tissue levels of active matrix metalloproteinase-2 and -9 in colorectal cancer.
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.
Waas
E T
ET
Department of Surgery, University Medical Centre St Radboud, Nijmegen PO Box 9101, 6500 HB, The Netherlands.
Lomme
R M L M
RM
DeGroot
J
J
Wobbes
Th
T
Hendriks
T
T
D002288:Adenocarcinoma, Mucinous / Q000201:enzymology* / Q000473:pathology; D000368:Aged; D002454:Cell Differentiation; D003106:Colon / Q000201:enzymology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011480:Protease Inhibitors / Q000378:metabolism
D011480:Protease Inhibitors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9