Evidence that high-migration drug-surviving MOLT4 leukemia cells exhibit cancer stem cell-like properties
Evidence that high-migration drug-surviving MOLT4 leukemia cells exhibit cancer stem cell-like properties
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高迁移药物存活的 MOLT4 白血病细胞表现出癌症干细胞样特性的证据
DOI：
10.3892/ijo.2016.3526
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发表时间：
2016-07-01
影响因子：
5.2
通讯作者：
Zhang, Qiuping
中科院分区：
文献类型：
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作者：
Huang, Xiaoxing;Xiong, Meng;Zhang, Qiuping
白血病是一系列威胁人类健康的血液恶性肿瘤。白血病的耐药和转移是患者死亡的主要原因。白血病干细胞（Leukemia stem cells，LSC）是白血病的始动细胞，也是白血病耐药、侵袭和转移的主要来源。因此，消除LSC是根除白血病的先决条件。本实验室的初步研究表明，趋化因子及其相关受体在白血病细胞的耐药性和转移中起重要作用。在本研究中，我们获得了高迁移药物存活（短期）MOLT 4细胞（hMDSCs-MOLT 4）与阿霉素（DOX）处理后，Transwell分析。采用流式细胞术、定量PCR、Western blotting、H&E染色和免疫组化等方法检测hMDSCs-MOLT 4细胞及其亲本细胞的干细胞相关分子标记。此外，我们还探讨了其对耐药性和肿瘤形成的影响。结果发现，与亲代MOLT 4细胞相比，hMDSCs-MOLT 4细胞中干细胞相关因子Sox 2、Oct 4、C-myc、Klf 4、Nanog、Bmi-1、CXCR 4的mRNA表达水平升高，Sox 2、Oct 4、Klf 4、Nanog、CXCR 4、CD 34的蛋白表达水平升高。我们的研究结果表明hMDSCs-MOLT 4细胞具有较强的耐药性和某些肿瘤干细胞样特征。这是第一个迹象表明，靶向干细胞因子如Sox 2，Oct 4，Klf 4，Nanog和CXCR 4可能代表消除T-ALL干细胞样细胞的合理选择。目前的研究结果阐明了耐药白血病细胞和癌症干细胞之间的关系。
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.