title: PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival.
abstract: The microvasculature consists of endothelial cells and their surrounding pericytes. Few studies on the regulatory mechanisms of tumour angiogenesis have focused on pericytes. Here we report the identification of tumour-derived PDGFRbeta (+) (platelet-derived growth factor receptor beta) progenitor perivascular cells (PPCs) that have the ability to differentiate into pericytes and regulate vessel stability and vascular survival in tumours. A subset of PDGFRbeta (+) PPCs is recruited from bone marrow to perivascular sites in tumours. Specific inhibition of PDGFRbeta signalling eliminates PDGFRbeta (+) PPCs and mature pericytes around tumour vessels, leading to vascular hyperdilation and endothelial cell apoptosis in pancreatic islet tumours of transgenic Rip1Tag2 mice.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Song
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ewald
authors.forename: William
authors.initials: W
authors.lastname: Stallcup
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
authors.forename: Gabriele
authors.initials: G
authors.lastname: Bergers
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001808:Blood Vessels / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D007340:Insulinoma / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000503:physiopathology; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D020286:Pericytes / Q000166:cytology / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D020797:Receptor, Platelet-Derived Growth Factor beta