Radiation therapy generates platelet-activating factor agonists

Ravi P. Sahu, Kathleen A. Harrison, Jonathan Weyerbacher, Robert C. Murphy, Raymond Konger, Joy Elizabeth Garrett, Helen Jan Chin-Sinex, Michael Edward Johnston, Joseph Dynlacht, Marc Mendonca, Kevin McMullen, Gengxin Li, Dan Spandau, Jeffrey Travers

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)20788-20800
Number of pages13
JournalOncotarget
Volume7
Issue number15
DOIs
StatePublished - Apr 12 2016

Keywords

  • Antioxidants
  • Cyclooxygenase type 2 enzyme
  • Oxidized glycerophosphocholines
  • Platelet-activating factor
  • Radiation therapy

ASJC Scopus subject areas

  • Oncology

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    Sahu, R. P., Harrison, K. A., Weyerbacher, J., Murphy, R. C., Konger, R., Garrett, J. E., Chin-Sinex, H. J., Johnston, M. E., Dynlacht, J., Mendonca, M., McMullen, K., Li, G., Spandau, D., & Travers, J. (2016). Radiation therapy generates platelet-activating factor agonists. Oncotarget, 7(15), 20788-20800. https://doi.org/10.18632/oncotarget.7878