The Telomerase Inhibitor Imetelstat Depletes Cancer Stem Cells in Breast and Pancreatic Cancer Cell Lines
The Telomerase Inhibitor Imetelstat Depletes Cancer Stem Cells in Breast and Pancreatic Cancer Cell Lines
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DOI：
10.1158/0008-5472.can-10-0233
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发表时间：
2010-11-15
期刊：
影响因子：
11.2
通讯作者：
Go, Ning F.
中科院分区：
文献类型：
--
作者：
Joseph, Immanual;Tressler, Robert;Go, Ning F.
癌症干细胞（CSC）是一种罕见的耐药癌细胞亚群，被认为是负责癌症和转移的维持和复发。端粒酶在肿瘤细胞和CSC中均具有组成性活性，但在正常组织中表达有限。因此，抑制端粒酶已被证明是一种可行的方法，在控制癌症生长的非临床研究，目前在第二阶段的临床试验。在这项研究中，我们研究了imetelstat（GRN163L），一种有效的端粒酶抑制剂，对散装癌细胞和推定的CSC的影响。当乳腺癌和胰腺癌细胞系在体外用伊美司他处理时，肿瘤细胞和CSC亚群中的端粒酶活性被抑制。此外，伊美司他处理减少了乳腺和胰腺细胞系中存在的CSC组分。在体外用伊美司他处理，而不是对照寡核苷酸，也降低了MCF 7乳腺球的增殖和自我更新潜力，并导致细胞死亡后，
Cancer stem cells (CSC) are rare drug-resistant cancer cell subsets proposed to be responsible for the maintenance and recurrence of cancer and metastasis. Telomerase is constitutively active in both bulk tumor cell and CSC populations but has only limited expression in normal tissues. Thus, inhibition of telomerase has been shown to be a viable approach in controlling cancer growth in nonclinical studies and is currently in phase II clinical trials. In this study, we investigated the effects of imetelstat (GRN163L), a potent telomerase inhibitor, on both the bulk cancer cells and putative CSCs. When breast and pancreatic cancer cell lines were treated with imetelstat in vitro, telomerase activity in the bulk tumor cells and CSC subpopulations were inhibited. Additionally, imetelstat treatment reduced the CSC fractions present in the breast and pancreatic cell lines. In vitro treatment with imetelstat, but not control oligonucleotides, also reduced the proliferation and self-renewal potential of MCF7 mammospheres and resulted in cell death after