Enhanced expression of stem cell markers and drug resistance in sphere-forming non-small cell lung cancer cells.

Enhanced expression of stem cell markers and drug resistance in sphere-forming non-small cell lung cancer cells.
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成球非小细胞肺癌细胞中干细胞标志物的表达增强和耐药性。

DOI:
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发表时间:
2015-06
期刊:
Int J Clin Exp Pathol
影响因子:
--
通讯作者:
Ye, Xiao-Qun
Ye, Xiao-Qun
中科院分区:
其他
文献类型:
--
作者:
Zhao, Ji-Hua;Chen, Sheng-Song;Song, Juan;Ye, Xiao-Qun

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越来越多的证据表明癌症干细胞(CSC)在肿瘤进展、转移和耐药性中发挥着关键作用。然而,CSC 在非小细胞肺癌 (NSCLC) 中的作用仍然难以捉摸。在这项研究中,我们从无血清培养基中培养的 NSCLC 细胞系 A549 衍生的肿瘤球中富集了干细胞样细胞。我们的结果表明,球体来源的细胞表达各种干细胞标记物,例如 CD44、CD133、Sox2 和 Oct4。与单层培养中的相应细胞相比,球体来源的细胞表现出明显的形态变化,并且干细胞标记物CD133的表达增加。此外,我们发现与 A549 贴壁细胞相比,球体来源的细胞表现出增加的增殖、细胞周期进展以及耐药特性。一致的是,几种耐药蛋白的表达,包括肺耐药相关蛋白(LRP)、谷胱甘肽-S-转移酶-π(GST-π)和多药耐药蛋白-1(MRP1)在球体来源的细胞中均显着增强。这些结果表明 CSC 在球形培养物中富集,并支持它们在调节 NSCLC 耐药性中的作用。
There is growing evidence suggesting that cancer stem cells (CSCs) are playing critical roles in tumor progression, metastasis and drug resistance. However, the role of CSCs in non-small cell lung cancer (NSCLC) remains elusive. In this study, we enriched for stem-like cells from tumor spheres derived from NSCLC cell line A549 cultured in serum-free medium. Our results showed that sphere-derived cells expressed various stem cell markers such as CD44, CD133, Sox2 and Oct4. Compared with the corresponding cells in monolayer cultures, sphere-derived cells showed marked morphologic changes and increased expression of the stem cell markers CD133. Furthermore, we found that sphere-derived cells exhibited increased proliferation, cell-cycle progression as well as drug-resistant properties as compared to A549 adherent cells. Consistently, expression of several drug resistance proteins, including lung resistance-related protein (LRP), glutathion-S-transferase-π (GST-π) and multidrug resistance proteins-1 (MRP1) were all significantly enhanced in sphere-derived cells. These results indicate the enrichment of CSCs in sphere cultures and support their role in regulating drug resistance in NSCLC.
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