The NADPH Oxidase Nox4 mediates tumour angiogenesis.
Acta Physiol (Oxf)
; 216(4): 435-46, 2016 Apr.
Article
en En
| MEDLINE
| ID: mdl-26513738
ABSTRACT
AIM:
The aim of this work was to identify the role of the NADPH oxidase Nox4 for tumour angiogenesis in a slow-growing tumour model in mice.METHODS:
Tumour angiogenesis was studied in tumours induced by the carcinogen 3-methylcholanthrene (MCA) in wild-type and Nox knockout mice. Mice were killed when the tumour reached a diameter of 1.5 cm and tumour tissue was used for histological and molecular analysis.RESULTS:
3-methylcholanthrene induced fibrosarcoma in wild-type, Nox1y/-, Nox2y/- and Nox4-/- mice. Histological analysis of vessel density using anti-CD31 staining showed a significant 38% reduction in tumour vascularization in fibrosarcomas of Nox4-/- mice. In contrast, tumour angiogenesis was doubled in Nox1 knockout mice, whereas knockout of Nox2 had no effect on tumour-vessel density. As underlying mechanisms, we identified a defect in hypoxia signalling in Nox4-/- mice. Hypoxia-inducible factor 1-alpha (Hif-1α) accumulation in the tumours was attenuated as was the expression of the Hif-1α-dependent pro-angiogenic genes vascular endothelial growth factor-A, glucose transporter 1 and adrenomedullin.CONCLUSION:
By regulating the tumour-vessel density through stabilization of Hif-1α and induction of VEGF expression, Nox4 promotes tumour angiogenesis and may represent a novel target for anti-angiogenic tumour therapy.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
NADPH Oxidasas
/
Neoplasias
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Neovascularización Patológica
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Acta Physiol (Oxf)
Asunto de la revista:
FISIOLOGIA
Año:
2016
Tipo del documento:
Article