title: Matrix metalloproteinase-2 and -9 in bile as a marker of liver metastasis in colorectal cancer.
abstract: Matrix metallproteinases (MMP)-2 and -9 are associated with cancer invasion and metastasis. MMP-2 and MMP-9 activities have never been assayed in bile. In the present study we investigated whether MMP-2 and -9 activities in the bile could be a marker for evaluation of liver metastasis in colorectal cancer. Fifty-three patients underwent colorectal resection for histologically verified adenocarcinoma. Twenty-six patients had colorectal cancer without liver metastasis and 27 patients had metastatic liver tumor. Six patients were studied as carcinoma-free control. MMP-2 and MMP-9 activities were assayed in bile using gelatin zymography and quantitated. Active MMP-2 activity of colorectal cancer with liver metastasis group (24.1 +/- 2.5 pixel count) was significantly higher than that of colorectal cancer without liver metastasis group (11.4 +/- 1.3 pixel count) (P < 0.001) or of control group (6.4 +/- 1.0 pixel count) (P < 0.001). Active MMP-9 was not detected in bile. ProMMP-9 activity of colorectal cancer with liver metastasis group (530.3 +/- 127.5 pixel count) was significantly higher than that of colorectal cancer without liver metastasis group (213.9 +/- 33.2 pixel count) (P = 0.008). This is the first report showing that the levels of active MMP-2 and proMMP-9 in bile were significantly higher in liver metastasis of colorectal cancer than in metastasis-free colorectal cancer. The results suggest that activities of active MMP-2 and proMMP-9 in the bile may be useful markers for predicting liver metastasis in colorectal cancer.
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Ishida
authors.forename: N
authors.initials: N
authors.lastname: Murata
authors.forename: D
authors.initials: D
authors.lastname: Hashimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Seyama
authors.forename: S
authors.initials: S
authors.lastname: Kubota
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000556:secondary; D000328:Adult; D000368:Aged; D001646:Bile / Q000201:enzymology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004796:Clinical Enzyme Tests; D017364:Collagenases / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000473:pathology*; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000556:secondary; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D004792:Enzyme Precursors; D017364:Collagenases; C120487:pro-matrix metalloproteinase 9; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9