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 -