Expression of vascular Notch ligands Delta-like 4 and Jagged-1 in glioblastoma.
Histopathology
; 60(5): 740-7, 2012 Apr.
Article
en En
| MEDLINE
| ID: mdl-22296176
ABSTRACT
AIMS:
The coordinated expression of the Notch ligands Delta-like 4 (Dll4) and Jagged (Jag)1 is believed to define appropriate endothelial sensitivity to vascular endothelial growth factor (VEGF). Preclinical data suggest that Dll4-Notch signalling may confer resistance to anti-VEGF therapy with bevacizumab, and Jag1 may antagonize Dll4-Notch. The aims of this study were to characterize the expression of Dll4 and Jag1 in primary glioblastomas. METHODS ANDRESULTS:
Immunohistochemistry was performed on 40 glioblastomas and normal brain using validated antibodies against Dll4 and Jag1. In-situ hybridization for Dll4 was performed on serial sections and compared with protein expression. Dll4 expression was localized to the cytoplasm and membrane of endothelial cells in all glioblastomas; it was weak or absent in normal brain. Jag1 expression was observed in the cytoplasm and membrane of glomeruloid and non-glomeruloid endothelial cells from 76% and 67% of glioblastomas, respectively. However, endothelial Jag1 expression was less intense and less prevalent than Dll4. There was no association between Dll4 and Jag1 expression.CONCLUSIONS:
In summary, Dll4 and Jag1 are expressed in glioblastoma vasculature. These data may define subsets of glioblastoma that might be sensitive (Dll4(+) /Jag1(+) ) or resistant (Dll4(+) /Jag1(-) ) to bevacizumab. Our data also suggest that anti-Dll4 therapy should be evaluated experimentally in glioblastoma.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
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Proteínas de Unión al Calcio
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Glioblastoma
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Péptidos y Proteínas de Señalización Intercelular
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Proteínas de la Membrana
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Histopathology
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido