The side population of ovarian cancer cells defines a heterogeneous compartment exhibiting stem cell characteristics.
The side population of ovarian cancer cells defines a heterogeneous compartment exhibiting stem cell characteristics.
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DOI：
10.18632/oncotarget.2053
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发表时间：
2014-08-30
期刊：
影响因子：
--
通讯作者：
Sopper S
中科院分区：
文献类型：
--
作者：
Boesch M;Zeimet AG;Reimer D;Schmidt S;Gastl G;Parson W;Spoeck F;Hatina J;Wolf D;Sopper S
癌症干细胞（CSC）被认为参与经典抗肿瘤疗法的肿瘤逃避，因此成为进一步改进抗癌策略的有吸引力的靶标。然而，CSC的存在和身份仍然存在争议。在对 13 种卵巢癌细胞系的系统筛选中，我们发现具有干细胞特性的细胞可以作为少数群体可靠地检测到，其特征是 ABC 转运蛋白表达导致侧群 (SP) 表型。在不同的细胞系中，ABCG2 或 ABCB1 被发现是造成这种效应的原因。纯化的 SP 细胞几乎具有真正 CSC 的所有特征，包括克隆形成性、不对称分裂和体内高致瘤性。通过多色流式细胞术进行深入表型分析，我们发现在所研究的卵巢癌细胞系中，SP区室表现出巨大的异质性，并且由多个表型不同的亚群组成。因此，我们的研究证实了先前的结果，即 CSC 包含在 SP 中。然而，CSC 的确切身份仍然被含有 CSC 的隔室的高度复杂性所掩盖。需要进一步的功能研究来确定单个细胞亚群是否可以明确定义为 CSC，或者具有不同特性的多个干细胞样细胞是否共存。此外，观察到的异质性可能反映了高度的可塑性，并可能影响肿瘤进展、逃避免疫监视和抗癌治疗耐药性的发展，因此在制定新的治疗策略时应予以考虑。
Cancer stem cells (CSC) are believed to be involved in tumor evasion of classical antitumor therapies and have thus become an attractive target for further improvement of anticancer strategies. However, the existence and identity of CSC are still a matter of controversy. In a systematic screen of 13 ovarian cancer cell lines we show that cells with stem cell properties are reliably detectable as a minor population, characterized by ABC transporter expression resulting in the side population (SP) phenotype. In different cell lines, either ABCG2 or ABCB1 was found to be responsible for this effect. Purified SP cells featured virtually all characteristics of bona fide CSC, including clonogenicity, asymmetric division and high tumorigenicity in vivo. Using in-depth phenotyping by multicolor flow cytometry, we found that among the investigated ovarian cancer cell lines the SP compartment exhibits tremendous heterogeneity and is composed of multiple phenotypically distinct subpopulations. Thus, our study confirms previous results showing that CSC are contained within the SP. However, the exact identity of the CSC is still disguised by the high complexity of the CSC-containing compartment. Further functional studies are needed to determine whether a single cellular subset can unambiguously be defined as CSC or whether multiple stem cell-like cells with different properties coexist. Moreover, the observed heterogeneity may reflect a high level of plasticity and likely influences tumor progression, escape from immune-surveillance and development of resistance to anticancer therapies and should therefore be considered in the development of new treatment strategies.
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影响因子：
16.6
作者：
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通讯作者：
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