Evidence for label-retaining tumour-initiating cells in human glioblastoma
Evidence for label-retaining tumour-initiating cells in human glioblastoma
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DOI：
10.1093/brain/awr081
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发表时间：
2011-05-01
期刊：
影响因子：
14.5
通讯作者：
Reynolds, Brent A.
中科院分区：
文献类型：
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作者：
Deleyrolle, Loic P.;Harding, Angus;Reynolds, Brent A.
单个肿瘤细胞在增殖率、细胞间相互作用、转移潜能和对治疗的敏感性方面表现出不同的功能行为。此外，测序研究表明，同一类型的单个患者肿瘤之间的遗传多样性水平令人惊讶。肿瘤的异质性是一个重大的治疗挑战，因为肿瘤内不同类型的细胞对治疗的反应可能不同，而患者之间的异质性可能会阻碍癌症一般治疗方法的发展。一种可能有助于克服肿瘤异质性的策略是识别驱动特定疾病病理的肿瘤亚群，以开发针对这些临床相关亚群的治疗方法。在这里，我们已经确定了一个保留染料的脑肿瘤群体，它显示了肿瘤启动亚群的所有特征。在免疫受损的小鼠中使用有限稀释移植试验，保留标记的脑肿瘤细胞显示出相对于总体人群更高的肿瘤起始特性。重要的是，从这些标记保留细胞产生的肿瘤表现出原发疾病的所有病理特征。总之，这些发现证实了保留染料的脑肿瘤细胞显示出肿瘤启动能力，因此是针对这一亚群的治疗方法开发的可行靶点。
Individual tumour cells display diverse functional behaviours in terms of proliferation rate, cell-cell interactions, metastatic potential and sensitivity to therapy. Moreover, sequencing studies have demonstrated surprising levels of genetic diversity between individual patient tumours of the same type. Tumour heterogeneity presents a significant therapeutic challenge as diverse cell types within a tumour can respond differently to therapies, and inter-patient heterogeneity may prevent the development of general treatments for cancer. One strategy that may help overcome tumour heterogeneity is the identification of tumour sub-populations that drive specific disease pathologies for the development of therapies targeting these clinically relevant sub-populations. Here, we have identified a dye-retaining brain tumour population that displays all the hallmarks of a tumour-initiating sub-population. Using a limiting dilution transplantation assay in immunocompromised mice, label-retaining brain tumour cells display elevated tumour-initiation properties relative to the bulk population. Importantly, tumours generated from these label-retaining cells exhibit all the pathological features of the primary disease. Together, these findings confirm dye-retaining brain tumour cells exhibit tumour-initiation ability and are therefore viable targets for the development of therapeutics targeting this sub-population.