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Updated: Jun 14, 2026

Preparation Of Neovascular Tissues from Human Glioma Tissues for Quantitative Proteomics Analysis of Tumor Angiogenesis
Published on: March 20, 2026
Increased ratio of vascular endothelial growth factor to semaphorin3A is a negative prognostic factor in human
Valeria Barresi1, Giovanni Tuccari1
1Department of Human Pathology, University of Messina, Messina, Italy.
Abstract:
Semaphorin3A (SEMA3A) is an anti-angiogenic factor which is expressed in human meningiomas in association with low microvessel density (MVD). It competes with vascular endothelial growth factor (VEGF) for receptor neuropilin-1 (NRP-1). The ratio between VEGF and SEMA3A has been recently demonstrated to regulate neo-angiogenesis, proliferation and progression of tumors. To clarify the involvement of these proteins in the above-mentioned phenomena, we analyzed the immunohistochemical expression of SEMA3A, VEGF and NRP-1 and their correlation with MVD in a series of 48 cases of meningioma with different histotype and histological grade. SEMA3A and VEGF expression was encountered in about half the cases, although at different levels. NRP-1 staining was evidenced in the vessels within all but two tumors and in the neoplastic cells of 18/48 meningiomas. A negative significant correlation emerged between SEMA3A amount and MVD; on the other hand, high VEGF levels appeared to be significantly associated with high MVD. A high VEGF/SEMA3A was significantly associated with high histological grade, proliferation index and MVD as well as with a higher recurrence rate of the meningiomas. Present data suggest that the balance between the expression of the pro-angiogenic factor VEGF and the anti-angiogenic SEMA3A may be involved in the regulation of neo-angiogenesis and proliferation in meningiomas, representing also a predictor of recurrences in these tumors. Further validation of our results may open the way for the use of drugs targeting not only VEGF, but also NRP-1 and SEMA3A to prevent recurrences of meningiomas.
Insights
The balance between vascular endothelial growth factor (VEGF) and Semaphorin3A (SEMA3A) impacts meningioma growth and recurrence. Targeting these factors may prevent tumor recurrence.
Area of Science:
- Oncology
- Molecular Biology
- Tumor Angiogenesis
Background:
- Semaphorin3A (SEMA3A) is an anti-angiogenic factor found in human meningiomas, inversely correlating with microvessel density (MVD).
- Vascular endothelial growth factor (VEGF) and SEMA3A compete for the receptor neuropilin-1 (NRP-1).
- The ratio of VEGF to SEMA3A influences tumor neo-angiogenesis, proliferation, and progression.
Purpose of the Study:
- To investigate the immunohistochemical expression of SEMA3A, VEGF, and NRP-1 in meningiomas.
- To correlate these protein expressions with microvessel density (MVD), histological grade, and recurrence rates.
- To elucidate the role of the VEGF/SEMA3A balance in meningioma pathogenesis.
Main Methods:
- Immunohistochemical analysis of SEMA3A, VEGF, and NRP-1 expression in 48 meningioma cases.
- Assessment of microvessel density (MVD) using standard histological techniques.
- Statistical correlation analysis between protein expression, MVD, histological grade, and recurrence.
Main Results:
- SEMA3A expression negatively correlated with MVD, while VEGF expression positively correlated with MVD.
- A high VEGF/SEMA3A ratio was significantly associated with higher histological grade, proliferation index, MVD, and increased recurrence rates.
- NRP-1 was detected in tumor vessels and neoplastic cells in a majority of cases.
Conclusions:
- The balance between VEGF and SEMA3A is crucial in regulating neo-angiogenesis and proliferation in meningiomas.
- The VEGF/SEMA3A ratio serves as a potential predictor of meningioma recurrence.
- Targeting VEGF, SEMA3A, and NRP-1 may offer novel therapeutic strategies for preventing meningioma recurrence.
