Evidence that high-migration drug-surviving MOLT4 leukemia cells exhibit cancer stem cell-like properties

Huang,Xiaoxing; Xiong,Meng; Jin,Yujie; Deng,Chaohua; Xu,Hui; An,Changqing; Hao,Ling; Yang,Xiangyong; Deng,Xinzhou; Tu,Zhenbo; Li,Xinran; Xiao,Ruijing; Zhang,Qiuping

doi:10.3892/ijo.2016.3526

Evidence that high-migration drug-surviving MOLT4 leukemia cells exhibit cancer stem cell-like properties

Authors:
- Xiaoxing Huang
- Meng Xiong
- Yujie Jin
- Chaohua Deng
- Hui Xu
- Changqing An
- Ling Hao
- Xiangyong Yang
- Xinzhou Deng
- Zhenbo Tu
- Xinran Li
- Ruijing Xiao
- Qiuping Zhang
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Affiliations: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Pediatrics, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei 430000, P.R. China, Hubei University of Technology Engineering and Technology College, Wuhan, Hubei 430000, P.R. China
Published online on: May 16, 2016 https://doi.org/10.3892/ijo.2016.3526
Pages: 343-351

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Abstract

Leukemia represents a spectrum of hematological malignancies threatening human health. Resistance to treatments and metastasis of leukemia are the main causes of death in patients. Leukemia stem cells (LSCs) are the initiating cells of leukemia as well as the main source of drug resistance, invasion and metastasis. Consequently, eliminating LSCs is a prerequisite to eradicate leukemia. Preliminary studies in our laboratory have shown that chemokines and their related receptors play an important role in the drug resistance and metastasis of leukemic cells. In this study, we obtained high migration drug-surviving (short term) MOLT4 cells (hMDSCs-MOLT4) with treatment of doxorubicin (DOX) after Transwell assay. Then we detected stem cell-associated molecular markers on hMDSCs-MOLT4 cells and the parental MOLT4 cells by FCM, QPCR, western blotting, H&E staining and immunohistochemistry experimental techniques in vitro and in vivo. Moreover, we explored its impact on drug resistance and tumor formation. Then we found that compared with the parental MOLT4 cells, the mRNA expression levels of stem cell-related factors Sox2, Oct4, C-myc, Klf4, Nanog, Bmi-1, CXCR4 are increased in hMDSCs-MOLT4 cells, together with the protein expression levels of Sox2, Oct4, Klf4, Nanog, CXCR4 and CD34. Our results indicated that hMDSCs-MOLT4 cells exhibited strong drug resistance and certain cancer stem cell-like characteristics. It is the first indication that the targeting stemness factors such as Sox2, Oct4, Klf4, Nanog and CXCR4 may represent plausible options for eliminating T-ALL stem-like cells. The present findings shed light on the relationship between drug-tolerant leukemic cells and cancer stem cells.

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