Glioblastoma Stem Cells Generate Vascular Pericytes to Support Vessel Function and Tumor Growth
Open accessAbstract
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.
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Glioblastoma stem cells are responsible for producing the majority of vascular pericytes to reshape the perivascular niche to support vascular function and tumor growth.
“analysis of human specimens has revealed that glioblastoma stem cells (GSCs) are responsible for producing the majority of vascular pericytes to reshape the perivascular niche to support vascular function and tumor growth.”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [35]
The Results section on primary human GBMs reports that most pericytes carried cancer-cell genetic alterations, supporting a neoplastic origin, but that analysis does not establish that they came specifically from GSCs. The Results on GBM xenografts and the Discussion support the GSC-origin and vessel-function claims; the citing sentence overattributes that conclusion to analysis of human specimens alone (page numbers unavailable). (LLM, conf=0.86)
Experimental — accuracy not yet measuredGSCs migrate along the SDF-1/CXCR4 axis toward endothelial cells, where they are transformed into pericytes mainly by the action of TGFβ.
“GSCs migrate along the SDF-1/CXCR4 axis toward the ECs, where they are transformed into pericytes mainly by the action of the transforming growth factor β (TGFβ) [35].”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [35]
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- Authors
- Cheng, L., Huang, Z., Zhou, W., Wu, Q., Donnola, S., Liu, J. K., Fang, X., Sloan, A. E., Mao, Y., Lathia, J. D., Min, W., McLendon, R. E., Rich, J. N., & Bao, S.
- Affiliations
- Cleveland Clinic (US)
- University Hospitals of Cleveland (US)
- Xiamen University (CN)
- Duke Medical Center (US)
- Corresponding author
- Bao, Shideng
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 153
- Issue
- 1
- Pages
- 139-152
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3638263
- OpenAlex
- W2026480865
- Cited by
- 905
- References
- 52
- Citations by year
- 2026: 34 · 2025: 51 · 2024: 52 · 2023: 68 · 2022: 77 · 2021: 97 · 2020: 86 · 2019: 66 · 2018: 69 · 2017: 73 · 2016: 54 · 2015: 75 · 2014: 66 · 2013: 35 · 2012: 1
- FWCI
- 34.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Foundation for the National Institutes of Health
- Cleveland Clinic Foundation
- National Heart, Lung, and Blood Institute (R01HL115148)
- National Institute of Neurological Disorders and Stroke (R01NS070315)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- glioblastoma, glioma stem cells, vascular pericytes, tumor vasculature, neovasculature, perivascular niche, mesenchymal differentiation, SDF-1/CXCR4 axis, TGF-beta, lineage tracing, tumor growth inhibition, anti-angiogenic therapy
- MeSH terms
- Animals, Brain, Brain Neoplasms, Cell Differentiation, Glioblastoma, Humans, Mice, Inbred BALB C, Mice, Nude, Neoplasm Transplantation, Transplantation, Heterologous, Neoplastic Stem Cells, Transforming Growth Factor beta, Pericytes, Endothelial Cells, Mice
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