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Updated: Aug 19, 2026
Preparation Of Neovascular Tissues from Human Glioma Tissues for Quantitative Proteomics Analysis of Tumor Angiogenesis
Published on: March 20, 2026
Expression and quantitative analysis of matrix metalloproteinase-2 and -9 in human gliomas
Kyoko Komatsu1, Yoko Nakanishi, Norimichi Nemoto
1Pathology Laboratory, Nihon University Itabashi Hospital, 30-1 Ohyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. kkoma@med.nihon-u.ac.jp
Abstract:
The matrix metalloproteinase (MMP) family members catalyze extracellular proteolysis. Recent reports have suggested that expression of MMP-2 and -9 might play a critical role in neoplastic tissue invasion or metastasis. In this study, the relationship between the expression of MMP-2 and -9 and the histological features of tissues from 21 cases of human glioma were investigated. MMP-2 and -9 proteins were detected by immnohistochemical studies. Amplification of MMP-2 and -9 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) assay. MMP-2 and -9 mRNA was measured quantitatively by the real-time RT-PCR method. Immunohistochemically, 38% of the cases were positive for MMP-2. Amplification of MMP-2 mRNA by RT-PCR was detected in 62% of the cases. There was no significant relationship between the expression of MMP-2 protein or mRNA and the biological nature of the tumors, including aggressiveness and histologic classification. The quantity of MMP-2 mRNA was 0.035 +/- 0.113 (MMP-2/GAPDH %), which was significantly elevated in cases of neoplastic dissemination or recurrence (P < 0.05). Tumor cells were immunohistochemically positive for MMP-9 in 81% of the samples. A positive reaction was found not only in neoplastic cells but also in endothelial cells, suggesting that the expression of MMP-9 protein might be associated with tumoral angiogenesis. The expression of mRNA in MMP-9 was detected in 91% of the cases, suggesting a close relationship between expression of MMP-9 and malignancy. The quantity of MMP-9 was 0.097 +/- 0.113 (MMP-9/GAPDH %) in all samples, which was significantly elevated in cases of glioblastoma (P < 0.05). The average Ki-67 labeling index was 8.14 +/- 5.26 in samples from G2 glioma, 19.92 +/- 11.29 in samples from G3 glioma, and 23.52 +/- 10.14 in samples from glioblastoma. All of the cases with elevated indices had recurrence or dissemination. The results of our study suggest that quantity analyses of MMP-2 and -9 mRNA and Ki-67 labeling index should be useful for discerning tumoral behaviors such as invasion, dissemination, and recurrence.
Insights
Matrix metalloproteinase (MMP)-2 and MMP-9 mRNA levels and Ki-67 index correlate with glioma behavior. Elevated MMP-2 and MMP-9 mRNA indicate neoplastic dissemination and malignancy, aiding in predicting tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) facilitate extracellular proteolysis.
- MMP-2 and MMP-9 expression is implicated in neoplastic invasion and metastasis.
Purpose of the Study:
- To investigate the relationship between MMP-2 and MMP-9 expression and histological features in human gliomas.
- To determine if MMP-2 and MMP-9 levels correlate with glioma aggressiveness, invasion, dissemination, and recurrence.
Main Methods:
- Immunohistochemistry to detect MMP-2 and MMP-9 proteins.
- Reverse transcription-polymerase chain reaction (RT-PCR) for MMP-2 and MMP-9 mRNA amplification.
- Real-time RT-PCR for quantitative analysis of MMP-2 and MMP-9 mRNA.
- Ki-67 labeling index assessment.
Main Results:
- MMP-2 mRNA quantity was significantly elevated in cases of neoplastic dissemination or recurrence (P < 0.05).
- MMP-9 protein expression was observed in neoplastic and endothelial cells, suggesting a role in angiogenesis.
- MMP-9 mRNA expression was closely linked to malignancy, with significantly elevated levels in glioblastoma (P < 0.05).
- Elevated Ki-67 labeling index correlated with tumor recurrence or dissemination.
Conclusions:
- Quantitative analysis of MMP-2 and MMP-9 mRNA, alongside the Ki-67 labeling index, can effectively discern tumoral behaviors like invasion, dissemination, and recurrence.
- These markers show promise for predicting glioma progression and guiding clinical management.
