Radiation therapy generates platelet-activating factor agonists
|Title||Radiation therapy generates platelet-activating factor agonists|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Sahu 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 Published||2016 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.