Article
The expression of candidate genes in endothelial proliferations defines the angiogenic switch in human gliomas
Die Expression von Kandidatengenen in endothelialen Proliferationen definiert den "angiogenic switch" in humanen Gliomen
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Published: | May 30, 2008 |
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Objective: Neoangiogenesis is a significant event in tumor growth. The former WHO classifications for gliomas described the angiogenesis to occur only in grade 4 tumors. Recent results showed that also WHO-grade 3 tumors may have pathological blood vessels. Because the exact time of the angiogenic switch is not known yet, we addressed the question when angiogenesis starts in glioma transformation to block its mechanisms.
Methods: We investigated 100 human gliomas for their microvessel density and for their expression of blood vessel markers like the endothelial surface molecule CD31 and the smooth muscle markers ASMA, HHF-35 and desmin. All experiments were done twice. 20 tissue specimens of autopsies served as negative controls. Statistical analysis was done with SPSS version 13.0 program.
Results: CD31 was expressed on the surface of all endothelial cells of physiological and pathological blood vessels. Desmin on the other hand, described in the biomedical literature as smooth muscle marker and as marker of pericytes, did not stain positive in human tissues at all. Only a very small subset of blood vessels outside the brain parenchyma was faintly positive for desmin. ASMA and HHF-35 stained different types of smooth muscle cells. Whereas ASMA stained smooth muscle cells in very small blood vessels (diameter<7µm), HHF-35 stained smooth muscle cells of greater blood vessels (diameter>7µm) only. Measurement of blood vessel density showed a decreased density in low-grade gliomas in comparison to healthy brain tissue. Blood vessel density increased stepwise in grade 3 gliomas and was highest in the glioblastoma group.
Conclusions: Desmin that is known as vascular smooth muscle marker in the literature does not work in human tissues, in comparison to its wide use in rodent glioma models. ASMA marks smaller blood vessels, whereas HHF-35 is expressed on smooth muscle cells of greater vessels. CD31 is positive on all endothelial cells and serves as internal control for overall vessel density. The blood vessel density rises from the WHO-grade 2 to the grade 3 gliomas ending in the grade 4 tumors. The start point of pathological neoangiogenesis is not found in the glioblastoma phase but much earlier when a WHO-grade 2 glioma transforms into a WHO-grade 3 glioma. This shows clearly that neoangiogenesis is not an exclusive feature of glioblastomas but is a constant indicator of grade 3 gliomas as well.