Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor
Shideng Bao,Qiulian Wu,Sith Sathornsumetee,Yueling Hao,Zhizhong Li,Anita B. Hjelmeland,Qing Shi,Roger E. McLendon,Darell D. Bigner,Jeremy N. Rich +9 more
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TLDR
Data indicate that stem cell-like tumor cells can be a crucial source of key angiogenic Factors in cancers and that targeting proangiogenic factors from stem cell -like tumor populations may be critical for patient therapy.Abstract:
Malignant gliomas are highly lethal cancers dependent on angiogenesis. Critical tumor subpopulations within gliomas share characteristics with neural stem cells. We examined the potential of stem cell-like glioma cells (SCLGC) to support tumor angiogenesis. SCLGC isolated from human glioblastoma biopsy specimens and xenografts potently generated tumors when implanted into the brains of immunocompromised mice, whereas non-SCLGC tumor cells isolated from only a few tumors formed secondary tumors when xenotransplanted. Tumors derived from SCLGC were morphologically distinguishable from non-SCLGC tumor populations by widespread tumor angiogenesis, necrosis, and hemorrhage. To determine a potential molecular mechanism for SCLGC in angiogenesis, we measured the expression of a panel of angiogenic factors secreted by SCLGC. In comparison with matched non-SCLGC populations, SCLGC consistently secreted markedly elevated levels of vascular endothelial growth factor (VEGF), which were further induced by hypoxia. In an in vitro model of angiogenesis, SCLGC-conditioned medium significantly increased endothelial cell migration and tube formation compared with non-SCLGC tumor cell-conditioned medium. The proangiogenic effects of glioma SCLGC on endothelial cells were specifically abolished by the anti-VEGF neutralizing antibody bevacizumab, which is in clinical use for cancer therapy. Furthermore, bevacizumab displayed potent antiangiogenic efficacy in vivo and suppressed growth of xenografts derived from SCLGC but limited efficacy against xenografts derived from a matched non-SCLGC population. Together these data indicate that stem cell-like tumor cells can be a crucial source of key angiogenic factors in cancers and that targeting proangiogenic factors from stem cell-like tumor populations may be critical for patient therapy.read more
Citations
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Glioma stem cells promote radioresistance by preferential activation of the DNA damage response
Shideng Bao,Qiulian Wu,Roger E. McLendon,Yueling Hao,Qing Ming Shi,Anita B. Hjelmeland,Mark W. Dewhirst,Darell D. Bigner,Jeremy N. Rich +8 more
TL;DR: This work shows that cancer stem cells contribute to glioma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity, and suggests that CD133-positive tumour cells could be the source of tumour recurrence after radiation.
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Malignant Gliomas in Adults
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TL;DR: The authors found that approximately 5% of patients with malignant gliomas have a family history of glioma and most of these familial cases are associated with rare genetic syndromes, such as neurofibromatosis types 1 and 2, the Li−Fraumeni syndrome (germ-line p53 mutations associated with an increased risk of several cancers), and Turcot's syndrome (intestinal polyposis and brain tumors).
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Cancer stem cells in solid tumours: accumulating evidence and unresolved questions
TL;DR: The cancer stem cell (CSC) hypothesis provides an attractive cellular mechanism to account for the therapeutic refractoriness and dormant behaviour exhibited by many of these tumours.
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The accessible chromatin landscape of the human genome
Robert E. Thurman,Eric Rynes,Richard Humbert,Jeff Vierstra,Matthew T. Maurano,Eric Haugen,Nathan C. Sheffield,Andrew B. Stergachis,Hao Wang,Benjamin Vernot,Kavita Garg,Sam John,Richard Sandstrom,Daniel Bates,Lisa Boatman,Theresa K. Canfield,Morgan Diegel,Douglas Dunn,Abigail K. Ebersol,Tristan Frum,Erika Giste,Audra K. Johnson,Ericka M. Johnson,Tanya Kutyavin,Bryan R. Lajoie,Bum Kyu Lee,Kristen Lee,Darin London,Dimitra Lotakis,Shane Neph,Fidencio Neri,Eric D. Nguyen,Hongzhu Qu,Hongzhu Qu,Alex Reynolds,Vaughn Roach,Alexias Safi,Minerva E. Sanchez,Amartya Sanyal,Anthony Shafer,Jeremy M. Simon,Lingyun Song,Shinny Vong,Molly Weaver,Yongqi Yan,Zhancheng Zhang,Zhuzhu Zhang,Boris Lenhard,Muneesh Tewari,Michael O. Dorschner,R. Scott Hansen,Patrick A. Navas,George Stamatoyannopoulos,Vishwanath R. Iyer,Jason D. Lieb,Shamil R. Sunyaev,Joshua M. Akey,Peter J. Sabo,Rajinder Kaul,Terrence S. Furey,Job Dekker,Gregory E. Crawford,John A. Stamatoyannopoulos,John A. Stamatoyannopoulos +63 more
TL;DR: The first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types is presented, revealing novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns.
Journal ArticleDOI
Malignant astrocytic glioma: genetics, biology, and paths to treatment.
Frank B. Furnari,Tim R. Fenton,Robert M. Bachoo,Akitake Mukasa,Jayne M. Stommel,Alexander H. Stegh,William C. Hahn,Keith L. Ligon,David N. Louis,Cameron Brennan,Lynda Chin,Ronald A. DePinho,Webster K. Cavenee +12 more
TL;DR: The recent confluence of advances in stem cell biology, cell signaling, genome and computational science and genetic model systems have revolutionized understanding of the mechanisms underlying the genetics, biology and clinical behavior of glioblastoma.
References
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Journal Article
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TL;DR: New findings in newly discovered vascular growth factors demand re-evaluation of therapeutic efforts aimed at regulating blood vessel growth in ischaemia, cancer and other pathological settings.
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Isolation and Characterization of Tumorigenic, Stem-like Neural Precursors from Human Glioblastoma
Rossella Galli,Elena Binda,Ugo Orfanelli,Barbara Cipelletti,Angela Gritti,Simona De Vitis,Roberta Fiocco,Chiara Foroni,Francesco DiMeco,Angelo L. Vescovi +9 more
TL;DR: It is reported that, unlike other brain cancers, the lethal glioblastoma multiforme contains neural precursors endowed with all of the critical features expected from neural stem cells.
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