The PTEN/PI3K/Akt pathway regulates stem-like cells in primary esophageal carcinoma cells

The PTEN/PI3K/Akt pathway regulates stem-like cells in primary esophageal carcinoma cells
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DOI:
10.4161/cbt.11.11.15531
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发表时间:
2011-06-01
影响因子:
3.6
通讯作者:
Lu, Shih Hsin
Lu, Shih Hsin
中科院分区:
医学3区
文献类型:
--
作者:
Li, Hongxia;Gao, Quanli;Lu, Shih Hsin

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最近的报告表明,癌症干细胞存在于许多恶性肿瘤中。侧群 (SP) 细胞用于富集许多细胞系和新鲜肿瘤标本中的癌症干细胞样细胞。在这项研究中,我们从食管鳞状细胞癌组织标本中培养了原发性食管鳞状细胞癌(ESCC)细胞。来自原代 ESCC 细胞的 SP 细胞比非 SP 细胞对化疗试剂具有更强的抵抗力,并且在体外形成更多的集落。此外,异种移植实验表明SP细胞在体内更具致瘤性。进一步的结果表明,PI3K/Akt 途径通过调节 ABCG2 转运蛋白功能对 SP 细胞至关重要。此外,发现 PTEN(而不是 mTOR)参与原代 ESCC 细胞中的 SP 细胞调节。这些发现表明,原代 ESCC 细胞中的 SP 细胞富含癌症干细胞样细胞,并且 PTEN/PI3K/Akt 通路调节这种干细胞样细胞群。这项研究表明,来自组织标本的原代培养细胞中的 SP 细胞可能成为癌症干细胞研究的有前景的模型,并可能帮助研究人员开发针对 ESCC 干细胞样细胞的新型治疗策略或有效药物。
Recent reports have shown that cancer stem cells exist in many malignancies. Side population (SP) cells are used to enrich cancer stem-like cells in many cell lines and fresh tumor specimens. In this study, we cultured primary esophageal squamous cell carcinoma (ESCC) cells from ESCC tissue specimens. SP cells from primary ESCC cells were more resistant to chemotherapeutic reagents and formed more colonies in vitro than non-SP cells. In addition, xenograft experiments revealed that SP cells were more tumorigenic in vivo. Further results indicated that the PI3K/Akt pathway is essential to SP cells through the regulation of ABCG2 transporter function. Furthermore, PTEN, rather than mTOR, was found to be involved in SP cell regulation in primary ESCC cells. These findings reveal that SP cells are enriched for cancer stem-like cells in primary ESCC cells and that the PTEN/PI3K/Akt pathway regulates this stem-like population. This study indicates that SP cells in primary culture cells from tissue specimens could be a promising model for cancer stem cell research and may help researchers develop novel therapeutic strategies or efficient drugs that target ESCC stem-like cells.