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Gene Expression of Matrix Metalloproteinases and their Inhibitors (TIMPs) in Meningiomas of Dogs
M T Mandara1, A Reginato1, G Foiani1
1Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
Background:
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are considered to be key mediators of tumor invasion and metastasis. MMP-2 and MMP-9 are expressed in meningiomas of dogs, but TIMP expression, and variations of specific MMP/TIMP ratios still are unknown in this tumor.
Hypothesis/Objectives:
Expression of MMP/TIMP might increase progressively from grade I to grade III meningioma. Therefore, genetic expression of MMP-2 and MMP-9, and specific TIMP-2 and TIMP-1, respectively, has been investigated in meningiomas of different grades.
Animals:
Selected formalin-fixed paraffin-embedded tissue from 43 meningiomas of dogs was evaluated.
Methods:
Genetic material was obtained from pathologic samples and used for quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR).
Results:
MMP-9 was not expressed in all of the tumors, but MMP-2 was significantly more expressed in papillary meningioma. Likewise, the MMP-2/TIMP-2 ratio was numerically higher in papillary meningiomas compared to all grades (>3.5 times) showing a strong bias in favor of metalloproteinase. In the papillary meningioma, TIMP-1 gene expression was significantly higher than in grades I and III.
Conclusions And Clinical Importance:
MMP-2/TIMP-2 imbalance might contribute to the aggressive biologic behavior of papillary meningiomas in dogs. TIMP-1 expression may play a role independent of MMP-9 expression in neoplastic progression. These results further support that therapeutic and prognostic evaluations of dogs with meningioma need to be addressed according to different histologic patterns as is performed in humans.
Insights
Matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) imbalances may drive aggressive papillary meningiomas in dogs. TIMP-1 expression also influences tumor progression, suggesting tailored treatment based on histologic patterns.
Area of Science:
- Veterinary Oncology
- Molecular Biology
- Cancer Research
Background:
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are crucial in tumor invasion and metastasis.
- MMP-2 and MMP-9 are found in canine meningiomas, but TIMP expression and MMP/TIMP ratios remain uncharacterized.
Purpose of the Study:
- To investigate the gene expression of MMP-2, MMP-9, TIMP-2, and TIMP-1 in canine meningiomas across different grades.
- To determine if MMP/TIMP expression increases with meningioma grade.
Main Methods:
- Analysis of 43 formalin-fixed paraffin-embedded canine meningioma tissues.
- Quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR) to assess gene expression.
Main Results:
- MMP-2 was significantly elevated in papillary meningiomas.
- The MMP-2/TIMP-2 ratio was substantially higher in papillary meningiomas, indicating a metalloproteinase bias.
- TIMP-1 expression was significantly higher in papillary meningiomas compared to grades I and III.
Conclusions:
- An MMP-2/TIMP-2 imbalance may contribute to the aggressive behavior of canine papillary meningiomas.
- TIMP-1 expression might independently affect neoplastic progression.
- Therapeutic and prognostic strategies for canine meningiomas should consider distinct histologic patterns, similar to human treatment approaches.
