In situ gelatinolytic activity correlates with tumor progression and prognosis in patients with bladder cancer.
OBJECTIVE
Degradation of the extracellular matrix by malignant tumor cells has an essential role in the process of tumor invasion and metastasis. The 2 gelatinolytic matrix metalloproteinases (MMPs) MMP-2 and MMP-9 are believed to be key enzymes in this process. We investigated the possible relationship between in situ gelatinolytic activity of MMPs and clinicopathological factors in patients with bladder cancer to clarify whether these proteins would be critical for tumor advancement in this disease.


METHODS
We evaluated the intensity of gelatinolytic activity in 25 bladder cancer tissues by film in situ zymography (FIZ). To clarify the MMP(s) responsible for gelatinolytic activity in bladder cancer tissues we examined MMP-2 and MMP-9 expression in bladder tissues by gelatin zymography. MMP expression was also confirmed by reverse transcriptase-polymerase chain reaction and Western blotting. We then investigated the association between MMP expression detected by gelatin zymography and the intensity of gelatinolytic activity determined by FIZ.


RESULTS
FIZ demonstrated that all tumor tissues had in situ gelatinolytic activities. There was a statistically significant correlation between the intensity of gelatinolytic activity, and tumor grade, stage, vessel invasion and cause specific survival (p <0.05). Stronger in situ gelatinolytic patterns were documented in cases with higher pro and active MMP-2 expression.


CONCLUSIONS
FIZ enables the direct assessment of in situ gelatinolytic activity in bladder cancer tissues. The intensity of activity appears to affect the biology of carcinoma tissues. Our results indicate a major role for MMP-2 in in situ gelatinolysis in bladder cancer.
Kawamura
Koji
K
Departments of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kamiya
Naoto
N
Suyama
Takahito
T
Shimbo
Masaki
M
Oosumi
Nobuyuki
N
Suzuki
Hiroyoshi
H
Ueda
Takeshi
T
Tobe
Toyofusa
T
Igarashi
Tatsuo
T
Ito
Haruo
H
Ishikura
Hiroshi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D017364:Collagenases / Q000378:metabolism; D018450:Disease Progression; D004792:Enzyme Precursors / Q000378:metabolism; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D005780:Gelatin / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery
D004792:Enzyme Precursors; D005780:Gelatin; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; C120487:pro-matrix metalloproteinase 9; C069860:progelatinase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9