PDGFR⁺ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival

Steven Song^1, 3, Andrew J. Ewald², William Stallcup⁵, Zena Werb^2, 4 & Gabriele Bergers^1, 3, 4

¹  Departments of Neurological Surgery, UCSF Comprehensive Cancer Center, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

²  Anatomy,UCSF Comprehensive Cancer Center, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

³  Brain Tumor Research Center, UCSF Comprehensive Cancer Center, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

⁴  UCSF Comprehensive Cancer Center, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

⁵  Cancer Research Center, Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

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 PDGFR ⁺ (platelet-derived growth factor receptor ) progenitor perivascular cells (PPCs) that have the ability to differentiate into pericytes and regulate vessel stability and vascular survival in tumours. A subset of PDGFR ⁺ PPCs is recruited from bone marrow to perivascular sites in tumours. Specific inhibition of PDGFR signalling eliminates PDGFR ⁺ PPCs and mature pericytes around tumour vessels, leading to vascular hyperdilation and endothelial cell apoptosis in pancreatic islet tumours of transgenic Rip1Tag2 mice.

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