Radiation therapy generates platelet-activating factor agonists.
Oncotarget
; 7(15): 20788-800, 2016 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-26959112
ABSTRACT
Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Raios Ultravioleta
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Fator de Ativação de Plaquetas
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Glicoproteínas da Membrana de Plaquetas
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Receptores Acoplados a Proteínas G
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Melanoma
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Antioxidantes
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article