Proliferation of vascular smooth muscle cells in glioblastoma multiforme

Laboratory investigation

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Object

Glioblastomas multiforme (GBM) contain a higher number of α-smooth muscle actin (SMA)–positive vascular smooth muscle cells (VSMCs) than those in the respective normal neuronal tissue. The role of VSMCs during angiogenesis is unclear, and it is also uncertain whether and to what extent angiogenic factors might be involved in GBM VSMCs. In GBMs, the contribution of VSMCs in angiogenesis accompanying endothelial proliferation and the correlation of VSMC proliferation with vascular endothelial growth factor (VEGF) expression were examined using an immunohistochemical method.

Methods

The examined material, including surrounding brain tissue, came from 12 cases (6 men and 6 women) with classic GBM. Microvessel densities (MVDs) of CD31-immunoreactive vessels (CD31-MVD) and SMA-immunoreactive vessels (SMA-MVD) were obtained in areas selected from white matter, boundary, tumor (concentrated area of tumor cells), and perinecrosis. Subsequently, the SMA-MVD/CD31-MVD (SMA/CD31) rate, representing the percentage of vessels with VSMCs in the region, was calculated in each area. The VEGF immunoreactivity of tumor cells was examined, and cases were divided into 2 groups: < 30% VEGF expression of tumor cells (low VEGF group) and > 30% VEGF expression of tumor cells (high VEGF group).

Results

The SMA/CD31 rate of the boundary was significantly lower than that of the tumor (p < 0.005) and perinecrosis (p < 0.001). The SMA/CD31 rate of the high VEGF group was significantly higher than that of the low VEGF group (p < 0.05) in the tumor.

Conclusions

In GBMs, the transformation and proliferation of VSMCs may accompany neovascularization and may also be induced by angiogenic factors.

Abbreviations used in this paper: DAB = 3, 3′-diaminobenzidine; EC = endothelial cells; GBM = glioblastoma multiforme; MVD = microvessel density; PDGF = platelet-derived growth factor; SMA = smooth muscle actin; VEGF = vascular endothelial growth factor; VSMC = vascular smooth muscle cell.
Article Information

Contributor Notes

Address correspondence to: Hiroaki Takeuchi, M.D., Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui, Japan 910-1193. email: takeu@u-fukui.ac.jp.Please include this information when citing this paper: published online November 20, 2009; DOI: 10.3171/2009.10.JNS08631.
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