Radiation therapy generates platelet-activating factor agonists

  • Posted on: 22 March 2016
  • By: fcoldren
TitleRadiation therapy generates platelet-activating factor agonists
Publication TypeJournal Article
Year of Publication2016
AuthorsSahu RP, Harrison KA, Weyerbacher J, Murphy RC, Konger RL, Garrett JElizabeth, Chin-Sinex HJan, Ii MEdward Joh, Dynlacht JR, Mendonca M, McMullen K, Li G, Spandau DF, Travers JB
Date Published2016 Mar 3

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.

Alternate JournalOncotarget
PubMed ID26959112