title: Antiangiogenic therapy inhibits the recruitment of vascular accessory cells to the perivascular niche in glioma angiogenesis.
abstract: OBJECTIVE
  Antiangiogenic therapies could be limited by various escape mechanisms including bone marrow-derived myeloid cell-induced vasculogenesis. The recruitment of vascular accessory cells (VACs) to the tumor neovasculature is as a multistep process. However, the recruitment process of these cells during antiangiogenic treatment remains unknown. The aim of our study was to characterize the recruitment of VACs during antiangiogenic therapy using sunitinib.
  
  
  METHODS
  C6 glioma cells were implanted into dorsal skinfold chambers. Animals received antiangiogenic therapy intraperitoneally for 5 days prior to VAC application intra-arterially. Intravital microscopy was performed during VAC injection and 1 and 48 h after injection. Analyses included total (TVD) and functional vessel densities (FVD), the perfusion index (PI), microvascular permeability, blood flow rate (Q), microvascular diameter (D), red blood cell velocity (RBCV), wall shear rate (γ), wall shear stress (τ), first and firm adhesions of VACs, and accumulation in the perivascular niche.
  
  
  RESULTS
  Antiangiogenic therapy resulted in a significant reduction in TVD (365 ± 47 cm/cm(2) vs. 183 ± 37 cm/cm(2)) and FVD (227 ± 65 cm/cm(2) vs. 147 ± 25 cm/cm(2)) and an increase in PI, Q, D, and RBCV. γ and τ remained unaltered. Initial adhesion and firm adhesion were unaffected by antiangiogenic therapy; however, the accumulation in the perivascular niche was significantly diminished in treated tumors (53.7 ± 8% vs. 24.0 ± 17%).
  
  
  CONCLUSIONS
  Antiangiogenic treatment inhibits the accumulation of VACs in the perivascular niche and therefore interferes with consecutive neovascularization.
authors.affiliation: Department of Neurosurgery, Universitätsmedizin Charité, Berlin, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Parmaksız
authors.forename: M
authors.initials: M
authors.lastname: Czabanka
authors.forename: M
authors.initials: M
authors.lastname: Vinci
authors.forename: P
authors.initials: P
authors.lastname: Vajkoczy
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D000077210:Sunitinib; D059016:Tumor Microenvironment
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib