Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

Schonberg David L.; Miller Tyler E.; Wu Qiulian; Flavahan William A.; Das Nupur K.; Hale James S.; Hubert Christopher G.; Mack Stephen C.; Jarrar Awad M.; Karl Robert T.; Rosager Ann Mari; Nixon Anne M.; Tesar Paul J.; Hamerlik Petra; Kristensen Bjarne W.; Horbinski Craig; Connor James R.; Fox Paul L.; Lathia Justin D.; Rich Jeremy N.

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Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

机译：优惠铁贩运表征胶质母细胞瘤干细胞

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摘要

Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue-specific progenitors. Direct interrogation of iron uptake demonstrated that CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin, two core iron regulators, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable dependence.

机译：Glioblastomas显示具有自我更新癌症干细胞（CSC）的层次结构。 RNA测序和增强剂映射显示了对CSC的调节程序，导致铁运输蛋白的上调，与组织特异性祖细胞的血液差异表达基因相比。直接询问铁摄取表明，CSCs比其他肿瘤细胞更有效地从微环境中提取铁。系统询问铁通量确定CSC优先需要转铁蛋白受体和铁蛋白，两种核心铁调节剂，在体内繁殖和形成肿瘤。耗尽铁蛋白通过STAT3-FOXM1调节轴破坏CSC有丝分裂进展，揭示了铁调节的CSC途径。铁是最早的寿命形式的独特原始金属基础，其中CSC具有表观规划的，可有价值的依赖。

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《Cancer Cell》 |2015年第4期|共15页
作者
Schonberg David L.; Miller Tyler E.; Wu Qiulian; Flavahan William A.; Das Nupur K.; Hale James S.; Hubert Christopher G.; Mack Stephen C.; Jarrar Awad M.; Karl Robert T.; Rosager Ann Mari; Nixon Anne M.; Tesar Paul J.; Hamerlik Petra; Kristensen Bjarne W.; Horbinski Craig; Connor James R.; Fox Paul L.; Lathia Justin D.; Rich Jeremy N.;
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作者单位

Cleveland Clin Dept Stem Cell Biol &

Regenerat Med Cleveland OH 44195 USA;

Cleveland Clin Dept Stem Cell Biol &

Regenerat Med Cleveland OH 44195 USA;

Cleveland Clin Dept Stem Cell Biol &

Regenerat Med Cleveland OH 44195 USA;

Cleveland Clin Dept Stem Cell Biol &

Regenerat Med Cleveland OH 44195 USA;

Cleveland Clin Dept Cellular &

Mol Med Cleveland OH 44195 USA;

Cleveland Clin Dept Cellular &

Mol Med Cleveland OH 44195 USA;

Cleveland Clin Dept Stem Cell Biol &

Regenerat Med Cleveland OH 44195 USA;

Cleveland Clin Dept Stem Cell Biol &

Regenerat Med Cleveland OH 44195 USA;

Cleveland Clin Dept Cellular &

Mol Med Cleveland OH 44195 USA;

Case Western Reserve Univ Sch Med Dept Genet &

Genome Sci Cleveland OH 44106 USA;

Odense Univ Hosp Dept Clin Pathol DK-5000 Odense Denmark;

Penn State Coll Med Dept Neurosurg Hershey PA 17033 USA;

Case Western Reserve Univ Sch Med Dept Genet &

Genome Sci Cleveland OH 44106 USA;

Danish Canc Soc Res Ctr Brain Tumor Biol Grp DK-2100 Copenhagen Denmark;

Odense Univ Hosp Dept Clin Pathol DK-5000 Odense Denmark;

Univ Kentucky Dept Pathol Div Neuropathol Lexington KY 40536 USA;

Penn State Coll Med Dept Neurosurg Hershey PA 17033 USA;

Cleveland Clin Dept Cellular &

Mol Med Cleveland OH 44195 USA;

Cleveland Clin Dept Cellular &

Mol Med Cleveland OH 44195 USA;

Cleveland Clin Dept Stem Cell Biol &

Regenerat Med Cleveland OH 44195 USA;

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正文语种 eng
中图分类肿瘤学;
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专利

1. Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells [J] . Schonberg David L., Miller Tyler E., Wu Qiulian, Cancer Cell . 2015,第4期

机译：优先铁贩运表征胶质母细胞瘤干样细胞
2. The Brain Microenvironment Preferentially Enhances the Radioresistance of CD133+ Glioblastoma Stem-like Cells [J] . Muhammad Jamal, Barbara H. Rath, Patricia S. Tsang, Neoplasia: an international journal for oncology research . 2012,第2期

机译：脑微环境优先增强CD133 +胶质母细胞瘤干细胞的辐射敏感度
3. MRI tracking of polyethylene glycol-coated superparamagnetic iron oxide-labelled placenta-derived mesenchymal stem cells toward glioblastoma stem-like cells in a mouse model [J] . Fei-Ting Hsu, Zung-Hang Wei, Yogi Chang-Yo Hsuan, Artificial cells, nanomedicine, and biotechnology. . 2018,第Suppa3期

机译：小鼠模型中聚乙二醇涂层的超顺磁性氧化铁标记的胎盘来源的间充质干细胞对成胶质细胞瘤干样细胞的MRI追踪
4. Identification of Cell Surface Glycoprotein Markers for Glioblastoma-derived Stem-like Cells Using a Lectin Microarray and LC-MS/MS Approach [C] . Jintang He, Yashu Liu, Xiaolei Xie, American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics . 2010

机译：使用凝集素微阵列和LC-MS / MS接近鉴定胶质母细胞瘤衍生瘤衍生的干细胞的细胞表面糖蛋白标志物
5. Natural Killer Cell-Based Immunotherapies Preferentially Target Stem-Like Cells. [D] . Ames, Erik. 2014

机译：基于自然杀伤细胞的免疫疗法优先靶向干细胞样细胞。
6. Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells [O] . David L. Schonberg, Tyler E. Miller, Qiulian Wu, -1

机译：优先铁贩运表征胶质母细胞瘤干细胞样细胞
7. Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells [O] . Schonberg, David L, Miller, Tyler E, Wu, Qiulian, 2015

机译：优先铁贩运表征胶质母细胞瘤干细胞样细胞

Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

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