A distinct "side population" of cells with high drug efflux capacity in human tumor cells
A distinct "side population" of cells with high drug efflux capacity in human tumor cells
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DOI：
10.1073/pnas.0400067101
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发表时间：
2004-09-28
影响因子：
11.1
通讯作者：
Brenner, MK
中科院分区：
文献类型：
--
作者：
Hirschmann-Jax, C;Foster, AE;Brenner, MK
干细胞的一个子集，称为“侧群”（SP），已被确定在哺乳动物物种的几个组织。这些细胞对抗有丝分裂药物保持高外排能力。我们已经研究了功能等同的干细胞是否也可以在人类癌症中检测到。我们最初检查了23例神经母细胞瘤患者的原发性肿瘤细胞和来自一系列其他肿瘤的细胞系。23例患者中有15例（65%）的神经母细胞瘤细胞中发现了明显的SP。SP能够离体持续扩增，并显示出不对称分裂的证据，产生SP和非SIP后代。这些细胞还表达高水平的ABCG 2和ABCA 3转运蛋白基因，并且具有更大的排出细胞毒性药物（如米托蒽醌）的能力，从而导致更好的存活。在乳腺癌、肺癌和胶质母细胞瘤细胞系中也检测到SP，这表明这种表型定义了一类对化疗药物具有固有高抗性的癌症干细胞，这些化疗药物应在恶性疾病的治疗期间被靶向。
A subset of stem cells, termed the "side population" (SP), has been identified in several tissues in mammalian species. These cells maintain a high efflux capability for antimitotic drugs. We have investigated whether functionally equivalent stem cells also may be detected in human cancers. We initially examined primary tumor cells from 23 patients with neuroblastoma and cell lines derived from a range of other tumors. A distinct SP was found in neuroblastoma cells from 15 of 23 patients (65%). The SP was capable of sustained expansion ex vivo and showed evidence for asymmetric division, generating both SP and non-SIP progeny. These cells also expressed high levels of ABCG2 and ABCA3 transporter genes and had a greater capacity to expel cytotoxic drugs, such as mitoxantrone, resulting in better survival. A SP also was detected in breast cancer, lung cancer, and glioblastoma cell lines, suggesting that this phenotype defines a class of cancer stem cells with inherently high resistance to chemotherapeutic agents that should be targeted during the treatment of malignant disease.