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Cancer Stem-Like Cells Enriched in Panc-1 Spheres Possess Increased Migration Ability and Resistance to Gemcitabine

机译:富含Panc-1球的癌症干细胞样细胞具有增加的迁移能力和对吉西他滨的耐药性

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摘要

Pancreatic cancer is one of the most lethal malignancies with poor prognosis. Previously, we found that a subpopulation of cancer stem cells (CSCs) in the Panc-1 pancreatic cancer cell line could propagate to form spheres. Here we characterized the malignant phenotypes of the pancreatic cancer stem CD44+/CD24+ cells, which were enriched under sphere forming conditions as analyzed by flow cytometry. These cells demonstrated increased resistance to gemcitabine and increased migration ability. Moreover, these cells exhibited epithelial to mesenchymal transition characterized by a decreased level of the epithelial marker E-cadherin and an increased level of the mesenchymal marker vimentin. Notably, abnormal expression of Bmi-1, ABCG2, Cyclin D1 and p16 were found in Panc-1 CSCs. Our results suggest that targeted inhibition of CSCs represents a novel therapeutic approach to overcome chemoresistance and metastasis of pancreatic cancer.
机译:胰腺癌是最致命的恶性肿瘤之一,预后不良。以前,我们发现Panc-1胰腺癌细胞系中的癌症干细胞(CSC)的亚群可以繁殖形成球体。在这里,我们表征了胰腺癌干CD44 + / CD24 +细胞的恶性表型,通过流式细胞术分析,其在球形形成条件下富集。这些细胞显示出对吉西他滨的增加的抵抗力和增加的迁移能力。此外,这些细胞表现出上皮到间质的转变,其特征在于上皮标记物E-钙粘着蛋白水平降低和间质标记物波形蛋白水平升高。值得注意的是,在Panc-1 CSC中发现了Bmi-1,ABCG2,Cyclin D1和p16的异常表达。我们的结果表明,靶向抑制CSCs代表了一种克服胰腺癌化学耐药性和转移的新型治疗方法。

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