Oncotarget

Research Papers:

Adipocytes cause leukemia cell resistance to daunorubicin via oxidative stress response

Xia Sheng, Jonathan Tucci, Jean-Hugues Parmentier, Lingyun Ji, James W. Behan, Nora Heisterkamp and Steven D. Mittelman _

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Oncotarget. 2016; 7:73147-73159. https://doi.org/10.18632/oncotarget.12246

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Abstract

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

Correspondence to:

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

ABSTRACT

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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