Exogenous APN protects normal tissues from radiation-induced oxidative damage and fibrosis in mice and prostate cancer patients with higher levels of APN have less radiation-induced toxicities
Joshua A. McDowell,
Elizabeth A. Kosmacek,
Michael J. Baine,
Oluwaseun Adebisi,
Cheng Zheng,
Madison M. Bierman,
Molly S. Myers,
Arpita Chatterjee,
Kia T. Liermann-Wooldrik,
Andrew Lim,
Kristin A. Dickinson,
Rebecca E. Oberley-Deegan
Affiliations
Joshua A. McDowell
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
Elizabeth A. Kosmacek
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
Michael J. Baine
Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
Oluwaseun Adebisi
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
Cheng Zheng
Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, 68198, USA
Madison M. Bierman
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
Molly S. Myers
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
Arpita Chatterjee
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
Kia T. Liermann-Wooldrik
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
Andrew Lim
College of Nursing, University of Nebraska Medical Center, Omaha, NE, 68198, USA
Kristin A. Dickinson
College of Nursing, University of Nebraska Medical Center, Omaha, NE, 68198, USA
Rebecca E. Oberley-Deegan
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Corresponding authorBCC 6Nebraska Medical Center, Omaha, NE, 68198, USA.
Radiation causes damage to normal tissues that leads to increased oxidative stress, inflammation, and fibrosis, highlighting the need for the selective radioprotection of healthy tissues without hindering radiotherapy effectiveness in cancer. This study shows that adiponectin, an adipokine secreted by adipocytes, protects normal tissues from radiation damage in vitro and in vivo. Specifically, adiponectin (APN) reduces chronic oxidative stress and fibrosis in irradiated mice. Importantly, APN also conferred no protection from radiation to prostate cancer cells. Adipose tissue is the primary source of circulating endogenous adiponectin. However, this study shows that adipose tissue is sensitive to radiation exposure exhibiting morphological changes and persistent oxidative damage. In addition, radiation results in a significant and chronic reduction in blood APN levels from adipose tissue in mice and human prostate cancer patients exposed to pelvic irradiation. APN levels negatively correlated with bowel toxicity and overall toxicities associated with radiotherapy in prostate cancer patients. Thus, protecting, or modulating APN signaling may improve outcomes for prostate cancer patients undergoing radiotherapy.
