Expression of Latent Matrix Metalloproteinase 9 (MMP-9) Predicts Survival in Advanced Ovarian Cancer

Lengyel, Ernst; Schmalfeldt, Barbara; Konik, Elisabeth; Späthe, Kerstin; Härting, Kathrin; Fenn, Anke; Berger, Ursula; Fridman, Rafael; Schmitt, Manfred; Prechtel, Dieter; Kuhn, Walther

doi:10.1006/gyno.2001.6243

Cited by 99 publications

(88 citation statements)

References 24 publications

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“…Brown found that active MMP-2 correlated with stage in NSCLC (Brown et al, 1993b) but not breast cancer (Brown et al, 1993a). Pro-MMP-9, but neither MMP-2 isoform, was associated with poor survival in both univariate and multivariate analyses in ovarian cancer (Lengyel et al, 2001). No relations were seen in bladder cancer (Papathoma et al, 2000), hepatocellular carcinoma (Maatta et al, 2000) or softtissue sarcomas (Maguire et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Upregulation of MMP-2 is seen in solid tumours including hepatocellular (Maatta et al, 2000), colorectal (Liabakk et al, 1996;Baker et al, 2000;Waas et al, 2002) and ovarian cancers (Lengyel et al, 2001). With regard to the relation of MMP activity, as assessed by gelatin zymography, with prognosis, results differ between studies and tumour types.…”

Section: Discussionmentioning

confidence: 99%

“…Reports using semiquantitative gelatin zymography have correlated MMP-2 and/or MMP-9 activity with survival and disease progression in several solid tumour types (Brown et al,1993b;Tokuraku et al, 1995;Ikebe et al, 1999;Papathoma et al, 2000;Lengyel et al, 2001;Di Nezza et al, 2002;Waas et al, 2002). The use of SDS in the buffers activates latent gelatinase isoforms, which enables assessment of both the latent (pro) and active bands of enzymatic activity.…”

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Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

et al. 2003

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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 ¼ 35), inflamed pleura (IP, n ¼ 12) and uninflammed pleura (UP, n ¼ 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 ¼ 0.006, Po0.001). Active MMP-2 was significantly greater in MM than in UP (P ¼ 0.04). MMP-2 activity was equivalent between IP and MM, but both pro-and active MMP-9 activities were greater in IP (P ¼ 0.02, P ¼ 0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P ¼ 0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P ¼ 0.03, total MMP-2 P ¼ 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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

et al. 2003

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“…The highest levels of the proteolytic factors were found in omental metastasis. An additional study by the same team of investigators showed that expression of the latent form of MMP-9 was an independent predictor of poor survival in patients with advanced ovarian cancer along with residual disease after optimal therapy [16].…”

Section: Therapeutic Approaches To Prevent Ovarian Cancer Relapsementioning

confidence: 99%

Future directions in the management of ovarian cancer

Disis

Rivkin²

2003

Hematology/Oncology Clinics of North America

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“…Matrix metalloproteinases (MMP), a family of 24 structurally related zinc-dependent endopeptidases, are capable of directly degrading essentially all components of the ECM (8,9) and thus are able to expose cryptic sites within the matrix molecules to activate other proteases, growth factors, and cytokines that may facilitate tumor invasion and metastasis. The role of several MMP family members, including MMP-2, MT1-MMP, and MMP-9, in EOC metastasis has been well documented (2,5,6,(10)(11)(12)(13)(14)(15). However, the role of matrilysin (MMP-7, pump-1) in EOC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Matrilysin Expression by Antisense or RNA Interference Decreases Lysophosphatidic Acid–Induced Epithelial Ovarian Cancer Invasion

Wang

Smicun

Calluzzo

et al. 2006

Molecular Cancer Research

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Our previous reports show that matrilysin [matrix metalloproteinase (MMP)-7] is overexpressed in epithelial ovarian cancer (EOC) and recombinant MMP-7 promotes EOC invasion in vitro. In the present study, we further evaluated the correlation of MMP-7 expression to EOC invasiveness and examined its role in lysophosphatidic acid (LPA)-induced invasion. By sense and antisense gene transfection in vitro, we show that overexpression of MMP-7 in all MMP-7 stably transfected DOV13 clones significantly enhanced their invasiveness, although MMP-7 antisense transfection caused a 91% decrease of MMP-7 expression (P < 0.01) and 87% decrease of invasion (P < 0.05) in geneticin (G418)-selected DOV13 clone P47-M7As-3 compared with vector-transfected control.As assessed by MMP-7 ELISA, LPA treatment at 10 to 80 Mmol/L significantly stimulated the secretion of total MMP-7 in DOV13 conditioned medium (P < 0.01). In addition, LPA apparently induced the activation of MMP-7 in DOV13 cells as detected by gelatin zymography. In the antisense MMP-7-transfected DOV13 clone (P47-M7As-3), LPA-increased invasion was significantly decreased compared with vector control. Moreover, knocking down of MMP-7 by small interfering RNA also suppressed LPA-induced invasion in two EOC cell lines (DOV13 and R182). Altogether, our results show that MMP-7 expression is correlated with EOC invasiveness and LPA-induced MMP-7 secretion/ activation may represent a new mechanism that facilitates ovarian cancer invasion besides the well-known induction of MT1-MMP-mediated proMMP-2 activation by LPA. (Mol Cancer Res 2006;4(11):831 -41)

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Expression of Latent Matrix Metalloproteinase 9 (MMP-9) Predicts Survival in Advanced Ovarian Cancer

Cited by 99 publications

References 24 publications

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Future directions in the management of ovarian cancer

Inhibition of Matrilysin Expression by Antisense or RNA Interference Decreases Lysophosphatidic Acid–Induced Epithelial Ovarian Cancer Invasion

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