title: Endogenous brain pericytes are widely activated and contribute to mouse glioma microvasculature.
abstract: 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.
authors: Lund Stem Cell Center, BMC B10, Skåne University Hospital, Lund, Sweden; Division of Neurosurgery, Department of Clinical Sciences, Skåne University Hospital, Lund, Sweden.
authors: Andreas
authors: A
authors: Svensson
authors: Translational Neurology Group, Division of Neurology, Department of Clinical Sciences, Wallenberg Neuroscience Center, Lund University and Skåne University Hospital, Lund, Sweden.
authors: Ilknur
authors: I
authors: Özen
authors: Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors: Guillem
authors: G
authors: Genové
authors: Translational Neurology Group, Division of Neurology, Department of Clinical Sciences, Wallenberg Neuroscience Center, Lund University and Skåne University Hospital, Lund, Sweden.
authors: Gesine
authors: G
authors: Paul
authors: Lund Stem Cell Center, BMC B10, Skåne University Hospital, Lund, Sweden; Division of Neurosurgery, Department of Clinical Sciences, Skåne University Hospital, Lund, Sweden.
authors: Johan
authors: J
authors: Bengzon
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000098:blood supply* / Q000473:pathology; D002448:Cell Adhesion; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005910:Glioma / Q000098:blood supply* / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D007797:Laminin / Q000378:metabolism; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D055806:Microvessels / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D020286:Pericytes / Q000378:metabolism / Q000473:pathology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D007797:Laminin; D049452:Green Fluorescent Proteins; D020797:Receptor, Platelet-Derived Growth Factor beta