Proliferation of Human Glioblastoma Stem Cells Occurs Independently of Exogenous Mitogens
Primary glial tumors of the central nervous system, most commonly glioblastoma multiforme (GBM), are aggressive lesions with a dismal prognosis. Despite identification and isolation of human brain tumor stem cells (BTSCs), characteristics that distinguish BTSCs from neural stem cells remain to be el...
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Published in | Stem cells (Dayton, Ohio) Vol. 27; no. 8; pp. 1722 - 1733 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.08.2009
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Subjects | |
Online Access | Get full text |
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Summary: | Primary glial tumors of the central nervous system, most commonly glioblastoma multiforme (GBM), are aggressive lesions with a dismal prognosis. Despite identification and isolation of human brain tumor stem cells (BTSCs), characteristics that distinguish BTSCs from neural stem cells remain to be elucidated. We cultured cells isolated from gliomas, using the neurosphere culture system, to understand their growth requirements. Both CD133+ and CD133− adult GBM BTSCs proliferated in the absence of exogenous mitogenic stimulation and gave rise to multipotent GBM spheres that were capable of self‐renewal. Epidermal growth factor (EGF) and fibroblast growth factor‐2 enhanced GBM BTSC survival, proliferation, and subsequent sphere size. Blockade of EGF receptor (EGFR) signaling reduced exogenous mitogen‐independent GBM sphere growth. Implantation of as few as 10 exogenous mitogen‐independent GBM BTSCs led to the formation of highly invasive intracranial tumors, which closely resembled human GBMs, in immunocompromised mice. These results demonstrate that exogenous mitogen independence, mediated in part through EGFR signaling, is one characteristic that distinguishes CD133+ and CD133− GBM BTSCs from neural stem cells. This novel experimental system will permit the elucidation of additional constitutively activated mechanisms that promote GBM BTSC survival, self‐renewal, and proliferation. STEM CELLS 2009;27:1722–1733 |
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Bibliography: | First published online in STEM CELLS April 23, 2009. Telephone: 403‐220‐3994; Fax: 403‐210‐9382 Author contributions: J.J.P.K.: Conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; O.S.: Conception and design, collection and/or assembly of data, data analysis and interpretation; A.C.: Conception and design, data analysis and interpretation, manuscript writing; X.L., J.F.D.: Collection and/or assembly of data, data analysis and interpretation; B.S.: Collection and/or assembly of data; D.L.S., R.N.A.: Conception and design, data analysis and interpretation; P.F.: Conception and design, financial support, data analysis and interpretation; J.G.C.: Conception and design, financial support, administrative support, data analysis and interpretation; I.F.P.: Conception and design, provision of study material or patients, financial support, data analysis and interpretation; S.W.: Conception and design, financial support, administrative support, data analysis and interpretation, manuscript writing, final approval of manuscript. EXPRESS ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1066-5099 1549-4918 |
DOI: | 10.1002/stem.98 |