Adipocytes cause leukemia cell resistance to daunorubicin via oxidative stress response

被引：50

作者：

Sheng, Xia ^{[1
]}

Tucci, Jonathan ^{[1
]}

Parmentier, Jean-Hugues ^{[1
]}

Ji, Lingyun ^{[2
]}

Behan, James W. ^{[1
]}

Heisterkamp, Nora ^{[3
,4
,5
]}

Mittelman, Steven D. ^{[1
,4
,6
,7
]}

机构：

[1] Childrens Hosp Los Angeles, Ctr Endocrinol Diabet & Metab, Diabet & Obes Program, Los Angeles, CA 90027 USA

[2] Childrens Hosp Los Angeles, Dept Biostat, Los Angeles, CA 90027 USA

[3] Childrens Hosp Los Angeles, Div Hematol Oncol & Bone Marrow Transplant, Los Angeles, CA 90027 USA

[4] Univ Southern Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA

[5] Univ Southern Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA USA

[6] Univ Southern Calif, Keck Sch Med, Dept Physiol, Los Angeles, CA 90033 USA

[7] Univ Southern Calif, Keck Sch Med, Dept Biophys, Los Angeles, CA 90033 USA

来源：

ONCOTARGET | 2016年 / 7卷 / 45期

关键词：

ALL; adipocyte; oxidative stress; glutathione; drug resistance; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ADIPOSE-TISSUE; CANCER-CELLS; TUMOR-GROWTH; DIFFERENTIATION; GLUTATHIONE; OBESITY; MICROENVIRONMENT; ADRENOMEDULLIN;

D O I：

10.18632/oncotarget.12246

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：73147 / 73159

页数：13

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