Forced extinction of CD24 stem-like breast cancer marker alone promotes radiation resistance through the control of oxidative stress
Forced extinction of CD24 stem-like breast cancer marker alone promotes radiation resistance through the control of oxidative stress
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DOI：
10.1002/mc.22273
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发表时间：
2016-03-01
影响因子：
4.6
通讯作者：
Lebeau, Jerome
中科院分区：
文献类型：
--
作者：
Bensimon, Julie;Biard, Denis;Lebeau, Jerome
沿着CD 44，CD 24是乳腺癌干细胞（CSC）的关键标志物，通常通过CD 24（-）/CD 44（+）标记来定义。在传统上归因于乳腺CD 24（-）/CD 44（+）癌细胞的所有表型中，辐射抗性已被广泛描述，并被视为与放射治疗失败有关。我们以前的资料表明，CD 24（-）细胞构成一个辐射抗性亚群暂时选择高剂量的电离辐射。然而，对CD 24在乳腺癌中的生物学作用知之甚少，也没有人认为CD 24在辐射反应中有任何功能。在此，在CD 24（-）细胞中诱导CD 24表达或在CD 24（+）细胞中敲低CD 24表达。我们发现，CD 24表达的强制消退与增殖率降低、活性氧（ROS）水平降低和基因组不稳定性降低相关。相反，当在CD 24（-）细胞中人工表达CD 24时，体外和体内增殖率、ROS水平和基因组不稳定性增强。此外，我们观察到，CD 24表达的损失导致辐射抗性，通过防止辐射诱导的细胞死亡和促进后代的产生与较低的G2/M阻滞和较小比例的多倍体细胞。最后，ROS水平的控制似乎是CD 24介导的辐射反应中的关键事件。首次提出CD 24作为乳腺癌细胞辐射反应的直接参与者，独立于CD 44表达。这些发现可能在评估原发性肿瘤的内在辐射反应方面具有有趣的应用。(c)2015 Wiley Periodicals，Inc.
Along with CD44, CD24 is a key marker of breast cancer stem cells (CSCs), frequently defined by CD24(-)/CD44(+) labeling. Among all phenotypes classically attributed to breast CD24(-)/CD44(+) cancer cells, radiation resistance has been extensively described and seen as being implicated in radiotherapy failure. Our previous data indicated that CD24(-) cells constitute a radiation-resistant subpopulation transitory selected by high doses of ionizing radiation. However, little is known about the biological role of CD24 in breast cancers, and no function has been assigned to CD24 in radiation response. Here, CD24 expression was induced in CD24(-) cells or knocked-down in CD24(+) cells. We show that forced extinction of CD24 expression is associated with decreased proliferation rate, lower levels of reactive oxygen species (ROS) and decreased genomic instability. On the opposite when CD24 is artificially expressed in CD24(-) cells, proliferation rates in vitro and in vivo, ROS levels and genomic instability are enhanced. Moreover, we observe that loss of CD24 expression leads to radiation resistance, by preventing radiation-induced cell death and promoting generation of progeny in relation to lower G2/M blockade and a smaller proportion of polyploid cells. Finally, control of ROS levels appears to be the key event in the CD24-mediated radiation response. For the first time, CD24 is proposed as a direct actor in radiation response of breast cancer cells, independently of CD44 expression. These findings could have interesting applications in evaluating the intrinsic radiation response of primary tumors. (c) 2015 Wiley Periodicals, Inc.