Glioblastoma Stem Cells Generate Vascular Pericytes to Support Vessel Function and Tumor Growth
By Lin Cheng, Zhi Huang, Wenchao Zhou, Qiulian Wu, S. Donnola, James K C Liu, X. Fang, A. Sloan, Y. Mao, J. Lathia and 4 more. Cell, 2013
852 citations recorded by the source corpus.
SUMMARY Glioblastomas (GBMs) are highly vascular and lethal brain tumors that display cellular hierarchies containing self-renewing tumorigenic glioma stem cells (GSCs). As GSCs often reside in perivascular niches and may undergo mensenchymal 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 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 induced to become pericytes predominantly by TGF-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 the anti-angiogenic therapy.
Subfields: Genetics, Neurology, Oncology
View Paper: https://www.semanticscholar.org/paper/4331b818a85c10e250d43c95d46dfab868b54e1e
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Citations in the corpus
- Tumor microenvironment complexity and therapeutic implications at a glance (2020, background): “In this report, activation of IL1/ leukemia inhibitory factor (LIF)/janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling generate inflammatory CAFs while TGFβ signaling antagonizes this process by downregulating interleukin 1 receptor, type I (IL1R1) expression and pr”
- Cancer stem cells in glioblastoma (2015, background): “CSCs also contribute to vascular structure through transdifferentiation into pericytes to promote tumor growth (Cheng et al. 2013).”
- Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions (2014, background): “pericytes, which may be a mechanism for vasculogenic mimicry [178–180].”