Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Expressions Correlate with the Recurrence of Intracranial Meningiomas

Okada, Masaki; Miyake, Keisuke; Matsumoto, Yoshihito; Kawai, Nobuyuki; Kunishio, Katsuzo; Nagao, Seigo

doi:10.1023/b:neon.0000013474.01161.58

Cited by 53 publications

(53 citation statements)

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“…MMP2 was generally very highly or highly expressed. This finding is consistent with previous reports suggesting their association with the potential to invade, especially increased levels of MMP2 and MMP9 in Grade 1 meningiomas as prognostic or predictive factors of recurrence (16,32). Moreover, in another study, the prognostic value of MMP9 in the risk of recurrence of meningiomas was investigated by analysing its expression in a series of meningiomas of different histological type and grade.…”

Section: Discussionsupporting

confidence: 91%

“…Similarly, MMP2 was also very highly expressed in all the snap frozen tissue samples (samples [13][14][15][16][17] and the majority of cultured cells (samples 1-12) whereas MMP9 was only highly expressed in 5 of the latter group (Fig. 1).…”

Section: Differential Expression Of Mmps and Timps In 17 Meningiomasmentioning

confidence: 92%

“…The expression of some MMPs has been well studied in gliomas (8)(9)(10)(11)(12) and meningiomas (13)(14)(15)(16)(17)(18)(19) particularly in relation to invasion or recurrence. Closely related to the MMPs is the ADAM (a disintegrin and metalloproteinase) family which has also been implicated in cancer, particularly via ADAMmediated activation of EGFR signalling (20).…”

Section: Introductionmentioning

confidence: 99%

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Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Rooprai

Martin

King

et al. 2016

International Journal of Oncology

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Abstract. MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of 8 ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence.

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Section: Discussionsupporting

confidence: 91%

Section: Differential Expression Of Mmps and Timps In 17 Meningiomasmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Rooprai

Martin

King

et al. 2016

International Journal of Oncology

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“…In human beings, 23.2% and 39.3% of meningiomas are reported to show a high expression of MMP-2 and MMP-9, respectively. 33 Whether the sample was taken as a biopsy or at necropsy does not seem to play a role in MMP-2 and MMP-9 expression either, suggesting that sampling time (in life or postmortem) is not a sufficient criterion to consider the biologic stage of the tumor. In fact, in our experience necropsy material does not always indicate the tumor with the most severe biologic behavior, because owners may request euthanasia because of a dramatic clinical progression or as soon as a cancer is diagnosed, thereby refusing support therapy or feasible surgery.…”

Section: Discussionmentioning

confidence: 99%

“…8,10 In our study we found that metalloproteinase expression is also independent of proliferative potential, as commonly observed in human meningiomas. 33 Only recently, a positive correlation was found between MMP-9 expression and proliferative index. 34 The proliferative index failed to be assessed by Ki67 expression in a number of cases, most likely due to a prolonged storage in formalin or in paraffin blocks responsible for subcellular modifications.…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Expression in Canine and Feline Meningioma

et al. 2009

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Abstract. Fifty-one meningiomas obtained from 28 dogs and 23 cats were selected for this study to investigate the immunohistochemical expression of matrix metalloproteinase (MMP)-2 and MMP-9 and to compare it to the reverse transcriptase subunit of human-telomerase, progesterone receptor expression, and the proliferative index of the tumors, expressed by Ki67 and proliferating cellular nuclear antigen. Paraffin-embedded tumor tissue was obtained from biopsy samples (28 cases) and at necropsy (23 cases). The most common histotype was malignant in dogs (12/28) and transitional in cats (12/23). Slides immunolabelled for MMPs showed a diffuse cytoplasmic pattern. Twenty-one cases (19 dogs and 2 cats) did not express MMP-2, while only 2 cases were completely negative for MMP-9. The highest values of MMP-2 and MMP-9 were observed in a psammomatous and meningothelial tumor, respectively. On statistical analysis, MMP-2 expression did not show a significant correlation with MMP-9. Moreover, both MMP expressions failed to show significant variance among histologic patterns of the tumor and correlation with the proliferative index. MMP immunolabeling showed an inconstant correlation with progesterone receptor expression. No significant correlation was found between MMP and reverse transcriptase subunit of human-telomerase expression. In feline meningiomas, the MMP-2 value was significantly higher than in canine tumors and the MMP-9 value tended to be low for meningiomas with a follow-up duration from the 23 rd month to the 44 th month. In cats, the longer the time from surgery, the lower the proliferative index seemed to be. In dogs, we failed to find a correlation between MMP expression and the follow-up duration.

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Increased expression of avian erythroblastosis virus E26 oncogene homolog 1 in World Health Organization grade 1 meningiomas is associated with an elevated risk of recurrence and is correlated with the expression of its target genes matrix metalloproteinase‐2 and MMP‐9

Okuducu

Zils

Michaelis

et al. 2006

Cancer

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BACKGROUND The transcription factor avian erythroblastosis virus E26 (V‐Ets) oncogene homolog 1 (Ets‐1) is involved in tumor development and progression through the transcriptional regulation of several matrix‐degrading enzyme systems, including matrix metalloproteinases (MMPs). It has been demonstrated that the MMPs are expressed strongly in high‐grade meningiomas. To determine the biologic significance of Ets‐1 in the progression of benign meningiomas, the authors investigated the expressions of Ets‐1 and its target genes MMP‐2 and MMP‐9 in primary and recurrent, Grade 1 meningiomas. METHODS The expression levels of Ets‐1, MMP‐2, and MMP‐9 were examined by immunohistochemistry in 70 Grade 1 meningiomas, including 36 primary tumors without recurrence after 5 years of follow‐up and 17 pairs of primary tumors and subsequent recurrences. RESULTS The results demonstrated higher expression of Ets‐1, MMP‐2, and MMP‐9 proteins in meningiomas with subsequent recurrences compared with meningiomas from patients who had no recurrences (P < .001). In addition, Ets‐1 expression was correlated with the expression of both MMP‐2 and MMP‐9. CONCLUSIONS Ets‐1 may be involved in meningioma recurrence by up‐regulating MMP‐2 and MMP‐9. Increased expression of these genes in World Health Organization grade 1 meningiomas may serve as an indicator for a high risk of recurrence. Cancer 2006. © 2006 American Cancer Society.

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Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Expressions Correlate with the Recurrence of Intracranial Meningiomas

Abstract: Our study indicated that MMP-2 and MMP-9 expressions are prognostic factors predicting the recurrence of meningioma, independent of proliferative potential.

Cited by 53 publications

References 24 publications

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Expression in Canine and Feline Meningioma

Increased expression of avian erythroblastosis virus E26 oncogene homolog 1 in World Health Organization grade 1 meningiomas is associated with an elevated risk of recurrence and is correlated with the expression of its target genes matrix metalloproteinase‐2 and MMP‐9

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