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Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth.

Publication ,  Journal Article
Cheng, L; Huang, Z; Zhou, W; Wu, Q; Donnola, S; Liu, JK; Fang, X; Sloan, AE; Mao, Y; Lathia, JD; Min, W; McLendon, RE; Rich, JN; Bao, S
Published in: Cell
March 28, 2013

Glioblastomas (GBMs) are highly vascular and lethal brain tumors that display cellular hierarchies containing self-renewing tumorigenic glioma stem cells (GSCs). Because GSCs often reside in perivascular niches and may undergo mesenchymal differentiation, we interrogated GSC potential to generate vascular pericytes. Here, we show that GSCs give rise to pericytes to support vessel function and tumor growth. In vivo cell lineage tracing with constitutive and lineage-specific fluorescent reporters demonstrated that GSCs generate the majority of vascular pericytes. Selective elimination of GSC-derived pericytes disrupts the neovasculature and potently inhibits tumor growth. Analysis of human GBM specimens showed that most pericytes are derived from neoplastic cells. GSCs are recruited toward endothelial cells via the SDF-1/CXCR4 axis and are induced to become pericytes predominantly by transforming growth factor β. Thus, GSCs contribute to vascular pericytes that may actively remodel perivascular niches. Therapeutic targeting of GSC-derived pericytes may effectively block tumor progression and improve antiangiogenic therapy.

Duke Scholars

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

March 28, 2013

Volume

153

Issue

1

Start / End Page

139 / 152

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Transforming Growth Factor beta
  • Pericytes
  • Neoplastic Stem Cells
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Humans
  • Glioblastoma
 

Citation

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Chicago
ICMJE
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Cheng, L., Huang, Z., Zhou, W., Wu, Q., Donnola, S., Liu, J. K., … Bao, S. (2013). Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell, 153(1), 139–152. https://doi.org/10.1016/j.cell.2013.02.021
Cheng, Lin, Zhi Huang, Wenchao Zhou, Qiulian Wu, Shannon Donnola, James K. Liu, Xiaoguang Fang, et al. “Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth.Cell 153, no. 1 (March 28, 2013): 139–52. https://doi.org/10.1016/j.cell.2013.02.021.
Cheng L, Huang Z, Zhou W, Wu Q, Donnola S, Liu JK, et al. Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell. 2013 Mar 28;153(1):139–52.
Cheng, Lin, et al. “Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth.Cell, vol. 153, no. 1, Mar. 2013, pp. 139–52. Pubmed, doi:10.1016/j.cell.2013.02.021.
Cheng L, Huang Z, Zhou W, Wu Q, Donnola S, Liu JK, Fang X, Sloan AE, Mao Y, Lathia JD, Min W, McLendon RE, Rich JN, Bao S. Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell. 2013 Mar 28;153(1):139–152.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

March 28, 2013

Volume

153

Issue

1

Start / End Page

139 / 152

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Transforming Growth Factor beta
  • Pericytes
  • Neoplastic Stem Cells
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Humans
  • Glioblastoma