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.
Highlights
Excess body weight contributes to as many as 1 out of 5 of all cancer-related deaths [1]
Obesity has shown to be associated with poorer event-free survival in the hematological cancer, acute lymphoblastic leukemia (ALL) [7,8,9], and we and others have demonstrated that leukemia/lymphoma cells can be found in close proximity to adipocytes in the bone marrow [10,11,12] and adipose tissue [13,14,15]
Given the significant protection that adipocytes provide to ALL cells, against the anthracycline daunorubicin (DNR) [16], we investigated whether adipocytes protect ALL cells from chemotherapies by relieving oxidative stress
Summary
Excess body weight contributes to as many as 1 out of 5 of all cancer-related deaths [1]. A landmark paper by Calle et al found a significant association between obesity and mortality from many types of cancer [2]. Many solid tumors reside in locations rich with adipocytes, including breast, ovarian, pancreatic, colon, and prostate cancers, and some studies have shown that adipocytes interact with cancer cells [3,4,5,6]. Obesity has shown to be associated with poorer event-free survival in the hematological cancer, acute lymphoblastic leukemia (ALL) [7,8,9], and we and others have demonstrated that leukemia/lymphoma cells can be found in close proximity to adipocytes in the bone marrow [10,11,12] and adipose tissue [13,14,15]. We investigate the role of adipocytes in alleviating oxidative stress caused by chemotherapy treatment in ALL cells
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