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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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 Date

  • March 28, 2013

Published In

Volume / Issue

  • 153 / 1

Start / End Page

  • 139 - 152

PubMed ID

  • 23540695

Pubmed Central ID

  • 23540695

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2013.02.021

Language

  • eng

Conference Location

  • United States