Adipocytes cause leukemia cell resistance to daunorubicin via oxidative stress response
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Xia Sheng1, Jonathan Tucci1, Jean-Hugues Parmentier1, Lingyun Ji2, James W. Behan1, Nora Heisterkamp3,4,5, Steven D. Mittelman1,4,6
1Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children’s Hospital Los Angeles, Los Angeles, CA, USA
2Department of Biostatistics, Children’s Hospital Los Angeles, Los Angeles, CA, USA
3Division of Hematology/Oncology and Bone Marrow Transplant, Children’s Hospital Los Angeles, Los Angeles, CA, USA
4Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
5Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
6Departments of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Steven D. Mittelman, email: [email protected]
Keywords: ALL, adipocyte, oxidative stress, glutathione, drug resistance
Received: February 11, 2016 Accepted: September 19, 2016 Published: September 26, 2016
Adipocytes promote cancer progression and impair treatment, and have been shown to protect acute lymphoblastic leukemia (ALL) cells from chemotherapies. Here we investigate whether this protection is mediated by changes in oxidative stress. Co-culture experiments showed that adipocytes protect ALL cells from oxidative stress induced by drugs or irradiation. We demonstrated that ALL cells induce intracellular ROS and an oxidative stress response in adipocytes. This adipocyte oxidative stress response leads to the secretion of soluble factors which protect ALL cells from daunorubicin (DNR). Collectively, our investigation shows that ALL cells elicit an oxidative stress response in adipocytes, leading to adipocyte protection of ALL cells against DNR.
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