title: Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura.
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.
authors.affiliation: University Department of Medical Oncology, Osborne Building, Leicester Royal Infirmary, Leicester LE1 5WW, UK.
authors.forename: J G
authors.initials: JG
authors.lastname: Edwards
authors.forename: J
authors.initials: J
authors.lastname: McLaren
authors.forename: J L
authors.initials: JL
authors.lastname: Jones
authors.forename: D A
authors.initials: DA
authors.lastname: Waller
authors.forename: K J
authors.initials: KJ
authors.lastname: O'Byrne
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies; D013534:Survival
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9