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Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura
Authors
AE Martin-Ucar
AH Drummond
+64 more
AJ Dickinson
AS Papathoma
B Nawrocki
BP Himelstein
CW Yorioka
D A Waller
D Bissett
D Cox
D Curran
DH Sterman
DJ Sugarbaker
DJ Sugarbaker
E Lengyel
E Tolnay
EA Baker
EA Baker
ET Waas
FA Attiga
G Cox
G Cox
G Cox
G Cox
G Karakiulakis
G Mautino
GA Finlay
GK Schwartz
H Bielefeldt-Ohmann
J Edwards
J G Edwards
J L Jones
J McLaren
J Pugin
JE Herndon
JG Edwards
JL Jones
K J O'Byrne
KJ O'Byrne
LA Di Nezza
M Maatta
M Polette
M Tokuraku
MR Pan
NB Liabakk
P Harvey
PD Brown
PD Brown
PD Maguire
R Kikuchi
R Maekawa
R Reich
S Abiru
S Kumar-Singh
S Kumar-Singh
SB Fox
SR Bramhall
SR Bramhall
T Ikebe
V Rusch
VB Antony
VW Rusch
W Steward
Y Ohta
YA DeClerck
Z Liu
Publication date
1 January 2003
Publisher
Nature Publishing Group
Doi
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PubMed
Abstract
Matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and -9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma (MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM (n = 35), inflamed pleura (IP, n = 12) and uninflammed pleura (UP, n = 14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan-Meier and Cox proportional hazard models. In MM, pro- and active MMP-2 levels were significantly greater than for MMP-9 (P = 0.006, P<0.001). Active MMP-2 was significantly greater in MM than in UP (P=0.04). MMP-2 activity was equivalent between IP and MM, but both pro- and active MMP-9 activities were greater in IP (P=0.02, P=0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P=0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P = 0.03, total MMP-2 P = 0.04). Total and pro-MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM. © 2003 Cancer Research UK
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oai:eprints.qut.edu.au:65046
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