Artikel
Widely accepted pericyte proteins are differentially expressed in human brain pericytes of healthy tissue from autopsy and glioma specimens of astrocytic lineage
Weithin akzeptierte Perizytenproteine werden in Perizyten von gesundem Hirngewebe von Autopsie-Serien und in Perizyten in humanen astrozytären Gliomen unterschiedlich exprimiert
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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
Text
Objective
Angiogenesis is a promising target in glioma therapy, especially in combined attacks against endothelial cells and pericytes (perivascular cells that stabilize microvessels). Here, we investigate pericyte morphology and expression of widely accepted pericyte proteins in human gliomas, to identify new targets for anti-angiogenesis.
Methods
19 gliomas, 4 brain specimens from autopsy, and skeletal muscle were incubated with primary antibodies against CD31, muscle actin isoform β (HHF-35), desmin, and α-smooth muscle actin (ASMA). Microscopy and volumetry were performed and statistically analysed by SPSS version 12.0.2.
Results
Expression of CD31 was up-regulated with increase of WHO grade. CD31 was positive in 25.09 (±11.43) blood vessels per low-power field (magnification 50x) in glioblastoma. This was different from astrocytoma grade III with 18.30 (±3.42) and astrocytoma grade II with only 10.92 (±3.95) vessels per low-power field. Autopsy brain tissue had a CD31 positivity of 20.05 (±4.32). ASMA immunoreactivity imitated the relative expression profile of CD31, but only in a subset of CD31 positive vessels. HHF-35 exhibited the same pattern of immunoreactivity in blood vessels of glioblastoma and autopsy tissue, but not in astrocytoma WHO grade III and II. Desmin did not stain microvessels at all. Skeletal muscle and fibroblasts of meninges were clearly positive. By estimation of vessel diameter, ASMA was mainly expressed in middle-sized microvessels and capillaries, whereas HHF-35 stained fewer capillaries and therefore fewer pericytes.
Conclusions
Two important conclusions are made. First, as indicated by CD31, healthy brain tissue is enlarged by low-grade astrocytoma causing greater distances between blood vessels, thereby reducing CD31 labelling index. With increasing malignancy, angiogenesis starts. But it starts not only in glioblastoma, but in to a very high degree in astrocytoma WHO grade III. This hypothesis is supported by ASMA immunoreactivity. Second, either ASMA or HHF-35 labelled just a subset of vessels in all tested tissues. It is not clear yet, whether negative blood vessels are free of pericytes or pericytes express other markers. Desmin did not stain microvessels at all, which is in considerable contrast to constant expression in pericytes of rodents. Follow-up experiments have to reveal the expression of further pericyte proteins like PDGFR-β or NG2 in vessel walls.