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 language | English (US) |
---|---|
Pages (from-to) | 20788-20800 |
Number of pages | 13 |
Journal | Oncotarget |
Volume | 7 |
Issue number | 15 |
DOIs | |
State | Published - Apr 12 2016 |
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Keywords
- Antioxidants
- Cyclooxygenase type 2 enzyme
- Oxidized glycerophosphocholines
- Platelet-activating factor
- Radiation therapy
ASJC Scopus subject areas
- Oncology
Cite this
Radiation therapy generates platelet-activating factor agonists. / Sahu, Ravi P.; Harrison, Kathleen A.; Weyerbacher, Jonathan; Murphy, Robert C.; Konger, Raymond; Garrett, Joy Elizabeth; Chin-Sinex, Helen Jan; Johnston, Michael Edward; Dynlacht, Joseph; Mendonca, Marc; McMullen, Kevin; Li, Gengxin; Spandau, Dan; Travers, Jeffrey.
In: Oncotarget, Vol. 7, No. 15, 12.04.2016, p. 20788-20800.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Radiation therapy generates platelet-activating factor agonists
AU - Sahu, Ravi P.
AU - Harrison, Kathleen A.
AU - Weyerbacher, Jonathan
AU - Murphy, Robert C.
AU - Konger, Raymond
AU - Garrett, Joy Elizabeth
AU - Chin-Sinex, Helen Jan
AU - Johnston, Michael Edward
AU - Dynlacht, Joseph
AU - Mendonca, Marc
AU - McMullen, Kevin
AU - Li, Gengxin
AU - Spandau, Dan
AU - Travers, Jeffrey
PY - 2016/4/12
Y1 - 2016/4/12
N2 - 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.
AB - 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.
KW - Antioxidants
KW - Cyclooxygenase type 2 enzyme
KW - Oxidized glycerophosphocholines
KW - Platelet-activating factor
KW - Radiation therapy
UR - http://www.scopus.com/inward/record.url?scp=84964699531&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964699531&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.7878
DO - 10.18632/oncotarget.7878
M3 - Article
C2 - 26959112
AN - SCOPUS:84964699531
VL - 7
SP - 20788
EP - 20800
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 15
ER -