Endogenous brain pericytes are widely activated and contribute to mouse glioma microvasculature

• Published in: PloS one 2015-04, Vol.10 (4), p.e0123553-e0123553
• Main Authors: Svensson, Andreas, Özen, Ilknur, Genové, Guillem, Paul, Gesine, Bengzon, Johan
• Format: Article
• Language: English
• Subjects: Adults; Angiogenesis; Animals; Astrocytes - metabolism; Astrocytes - pathology; Biomarkers, Tumor - metabolism; Brain; Brain - pathology; Brain cancer; Brain Neoplasms - blood supply; Brain Neoplasms - pathology; Brain tumors; Cell Adhesion; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; Clinical Medicine; Cortex; Female; Fluorescence; Glioblastoma; Glioblastoma multiforme; Glioma; Glioma - blood supply; Glioma - pathology; Gliomas; Green fluorescent protein; Green Fluorescent Proteins - metabolism; Growth factors; Hypoxia; Inflammation - pathology; Klinisk medicin; Laminin - metabolism; Medical and Health Sciences; Medicin och hälsovetenskap; Mice, Inbred C57BL; Microglia - metabolism; Microglia - pathology; Microvasculature; Microvessels - pathology; Neovascularization; Neovascularization, Pathologic - pathology; Neurologi; Neurology; Neuronal-glial interactions; Neurosciences; Neurosurgery; Pericytes; Pericytes - metabolism; Pericytes - pathology; Phenotypes; Platelet-derived growth factor; Proteins; Receptor, Platelet-Derived Growth Factor beta - metabolism; Stem cells; Stromal Cells - metabolism; Stromal Cells - pathology; Subventricular zone; Tumors; Vascularization
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0123553

Glioblastoma multiforme (GBM) is the most common brain tumor in adults. It presents an extremely challenging clinical problem, and treatment very frequently fails due to the infiltrative growth, facilitated by extensive angiogenesis and neovascularization. Pericytes constitute an important part of the GBM microvasculature. The contribution of endogenous brain pericytes to the tumor vasculature in GBM is, however, unclear. In this study, we determine the site of activation and the extent of contribution of endogenous brain pericytes to the GBM vasculature. GL261 mouse glioma was orthotopically implanted in mice expressing green fluorescent protein (GFP) under the pericyte marker regulator of G protein signaling 5 (RGS5). Host pericytes were not only activated within the glioma, but also in cortical areas overlying the tumor, the ipsilateral subventricular zone and within the hemisphere contralateral to the tumor. The host-derived activated pericytes that infiltrated the glioma were mainly localized to the tumor vessel wall. Infiltrating GFP positive pericytes co-expressed the pericyte markers platelet-derived growth factor receptor-β (PDGFR-β) and neuron-glial antigen 2. Interestingly, more than half of all PDGFR-β positive pericytes within the tumor were contributed by the host brain. We did not find any evidence that RGS5 positive pericytes adopt another phenotype within glioma in this paradigm. We conclude that endogenous pericytes become activated in widespread areas of the brain in response to an orthotopic mouse glioma. Host pericytes are recruited into the tumor and constitute a major part of the tumor pericyte population.