Glioblastoma stem-like cells give rise to tumour endothelium.
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| Title: | Glioblastoma stem-like cells give rise to tumour endothelium. |
|---|---|
| Authors: | Rong Wang, Chadalavada, Kalyani, Wilshire, Jennifer, Kowalik, Urszula, Hovinga, Koos E., Geber, Adam, Fligelman, Boris, Leversha, Margaret, Brennan, Cameron, Tabar, Viviane |
| Source: | Nature. 12/9/2010, Vol. 468 Issue 7325, p829-833. 5p. 4 Graphs. |
| Subjects: | Glioblastoma multiforme, Endothelial growth factors, Neovascularization, Antibody diversity, Comparative genomic hybridization, Stem cells |
| Abstract: | Glioblastoma (GBM) is among the most aggressive of human cancers. A key feature of GBMs is the extensive network of abnormal vasculature characterized by glomeruloid structures and endothelial hyperplasia. Yet the mechanisms of angiogenesis and the origin of tumour endothelial cells remain poorly defined. Here we demonstrate that a subpopulation of endothelial cells within glioblastomas harbour the same somatic mutations identified within tumour cells, such as amplification of EGFR and chromosome 7. We additionally demonstrate that the stem-cell-like CD133+ fraction includes a subset of vascular endothelial-cadherin (CD144)-expressing cells that show characteristics of endothelial progenitors capable of maturation into endothelial cells. Extensive in vitro and in vivo lineage analyses, including single cell clonal studies, further show that a subpopulation of the CD133+ stem-like cell fraction is multipotent and capable of differentiation along tumour and endothelial lineages, possibly via an intermediate CD133+/CD144+ progenitor cell. The findings are supported by genetic studies of specific exons selected from The Cancer Genome Atlas, quantitative FISH and comparative genomic hybridization data that demonstrate identical genomic profiles in the CD133+ tumour cells, their endothelial progenitor derivatives and mature endothelium. Exposure to the clinical anti-angiogenesis agent bevacizumab or to a ?-secretase inhibitor as well as knockdown shRNA studies demonstrate that blocking VEGF or silencing VEGFR2 inhibits the maturation of tumour endothelial progenitors into endothelium but not the differentiation of CD133+ cells into endothelial progenitors, whereas ?-secretase inhibition or NOTCH1 silencing blocks the transition into endothelial progenitors. These data may provide new perspectives on the mechanisms of failure of anti-angiogenesis inhibitors currently in use. The lineage plasticity and capacity to generate tumour vasculature of the putative cancer stem cells within glioblastoma are novel findings that provide new insight into the biology of gliomas and the definition of cancer stemness, as well as the mechanisms of tumour neo-angiogenesis. [ABSTRACT FROM AUTHOR] |
| Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 55774489 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Glioblastoma stem-like cells give rise to tumour endothelium. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Rong+Wang%22">Rong Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Chadalavada%2C+Kalyani%22">Chadalavada, Kalyani</searchLink><br /><searchLink fieldCode="AR" term="%22Wilshire%2C+Jennifer%22">Wilshire, Jennifer</searchLink><br /><searchLink fieldCode="AR" term="%22Kowalik%2C+Urszula%22">Kowalik, Urszula</searchLink><br /><searchLink fieldCode="AR" term="%22Hovinga%2C+Koos+E%2E%22">Hovinga, Koos E.</searchLink><br /><searchLink fieldCode="AR" term="%22Geber%2C+Adam%22">Geber, Adam</searchLink><br /><searchLink fieldCode="AR" term="%22Fligelman%2C+Boris%22">Fligelman, Boris</searchLink><br /><searchLink fieldCode="AR" term="%22Leversha%2C+Margaret%22">Leversha, Margaret</searchLink><br /><searchLink fieldCode="AR" term="%22Brennan%2C+Cameron%22">Brennan, Cameron</searchLink><br /><searchLink fieldCode="AR" term="%22Tabar%2C+Viviane%22">Tabar, Viviane</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Nature%22">Nature</searchLink>. 12/9/2010, Vol. 468 Issue 7325, p829-833. 5p. 4 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Glioblastoma+multiforme%22">Glioblastoma multiforme</searchLink><br /><searchLink fieldCode="DE" term="%22Endothelial+growth+factors%22">Endothelial growth factors</searchLink><br /><searchLink fieldCode="DE" term="%22Neovascularization%22">Neovascularization</searchLink><br /><searchLink fieldCode="DE" term="%22Antibody+diversity%22">Antibody diversity</searchLink><br /><searchLink fieldCode="DE" term="%22Comparative+genomic+hybridization%22">Comparative genomic hybridization</searchLink><br /><searchLink fieldCode="DE" term="%22Stem+cells%22">Stem cells</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Glioblastoma (GBM) is among the most aggressive of human cancers. A key feature of GBMs is the extensive network of abnormal vasculature characterized by glomeruloid structures and endothelial hyperplasia. Yet the mechanisms of angiogenesis and the origin of tumour endothelial cells remain poorly defined. Here we demonstrate that a subpopulation of endothelial cells within glioblastomas harbour the same somatic mutations identified within tumour cells, such as amplification of EGFR and chromosome 7. We additionally demonstrate that the stem-cell-like CD133+ fraction includes a subset of vascular endothelial-cadherin (CD144)-expressing cells that show characteristics of endothelial progenitors capable of maturation into endothelial cells. Extensive in vitro and in vivo lineage analyses, including single cell clonal studies, further show that a subpopulation of the CD133+ stem-like cell fraction is multipotent and capable of differentiation along tumour and endothelial lineages, possibly via an intermediate CD133+/CD144+ progenitor cell. The findings are supported by genetic studies of specific exons selected from The Cancer Genome Atlas, quantitative FISH and comparative genomic hybridization data that demonstrate identical genomic profiles in the CD133+ tumour cells, their endothelial progenitor derivatives and mature endothelium. Exposure to the clinical anti-angiogenesis agent bevacizumab or to a ?-secretase inhibitor as well as knockdown shRNA studies demonstrate that blocking VEGF or silencing VEGFR2 inhibits the maturation of tumour endothelial progenitors into endothelium but not the differentiation of CD133+ cells into endothelial progenitors, whereas ?-secretase inhibition or NOTCH1 silencing blocks the transition into endothelial progenitors. These data may provide new perspectives on the mechanisms of failure of anti-angiogenesis inhibitors currently in use. The lineage plasticity and capacity to generate tumour vasculature of the putative cancer stem cells within glioblastoma are novel findings that provide new insight into the biology of gliomas and the definition of cancer stemness, as well as the mechanisms of tumour neo-angiogenesis. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/nature09624 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 5 StartPage: 829 Subjects: – SubjectFull: Glioblastoma multiforme Type: general – SubjectFull: Endothelial growth factors Type: general – SubjectFull: Neovascularization Type: general – SubjectFull: Antibody diversity Type: general – SubjectFull: Comparative genomic hybridization Type: general – SubjectFull: Stem cells Type: general Titles: – TitleFull: Glioblastoma stem-like cells give rise to tumour endothelium. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Rong Wang – PersonEntity: Name: NameFull: Chadalavada, Kalyani – PersonEntity: Name: NameFull: Wilshire, Jennifer – PersonEntity: Name: NameFull: Kowalik, Urszula – PersonEntity: Name: NameFull: Hovinga, Koos E. – PersonEntity: Name: NameFull: Geber, Adam – PersonEntity: Name: NameFull: Fligelman, Boris – PersonEntity: Name: NameFull: Leversha, Margaret – PersonEntity: Name: NameFull: Brennan, Cameron – PersonEntity: Name: NameFull: Tabar, Viviane IsPartOfRelationships: – BibEntity: Dates: – D: 09 M: 12 Text: 12/9/2010 Type: published Y: 2010 Identifiers: – Type: issn-print Value: 00280836 Numbering: – Type: volume Value: 468 – Type: issue Value: 7325 Titles: – TitleFull: Nature Type: main |
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