Glioblastoma Stem Cells Generate Vascular Pericytes to Support Vessel Function and Tumor Growth
Menée in vivo et sur des échantillons tumoraux prélevés sur des patients atteints d'un glioblastome, cette étude met en évidence le rôle joué par des cellules souches de glioblastome dans la formation de péricytes qui, en remodelant le réseau vasculaire, favorisent la progression tumorale
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 ². 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. º Glioblastoma stem cells (GSCs) generate vascular pericytes to maintain tumor vessels º Targeting GSC-derived pericytes disrupts vessel function and inhibits tumor growth º GSCs are recruited to the perivascular niche via SDF-1-CXCR4 signaling º Transforming growth factor ² predominantly promotes GSCs to assume a pericyte lineage In vivo lineage tracing shows that glioblastoma stem cells (GSCs) give rise to vascular pericytes cells that support vessel function and hence promote tumor growth and that targeting of GSC-derived pericytes inhibits the growth of these highly vascular and lethal brain tumors.