title: Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth.
abstract: 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.
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.forename: Zhi
authors.initials: Z
authors.lastname: Huang
authors.forename: Wenchao
authors.initials: W
authors.lastname: Zhou
authors.forename: Qiulian
authors.initials: Q
authors.lastname: Wu
authors.forename: Shannon
authors.initials: S
authors.lastname: Donnola
authors.forename: James K
authors.initials: JK
authors.lastname: Liu
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Fang
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Sloan
authors.forename: Yubin
authors.initials: Y
authors.lastname: Mao
authors.forename: Justin D
authors.initials: JD
authors.lastname: Lathia
authors.forename: Wang
authors.initials: W
authors.lastname: Min
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Rich
authors.forename: Shideng
authors.initials: S
authors.lastname: Bao
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology*; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000473:pathology; D005909:Glioblastoma / Q000098:blood supply / Q000473:pathology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D020286:Pericytes / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D016212:Transforming Growth Factor beta
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