title: Improved functionality of the vasculature during conventionally fractionated radiation therapy of prostate cancer.
abstract: Although endothelial cell apoptosis participates in the tumor shrinkage after single high-dose radiotherapy, little is known regarding the vascular response after conventionally fractionated radiation therapy. Therefore, we evaluated hypoxia, perfusion and vascular microenvironment changes in an orthotopic prostate cancer model of conventionally fractionated radiation therapy at clinically relevant doses (2 Gy fractions, 5 fractions/week). First, conventionally fractionated radiation therapy decreased tumor cell proliferation and increased cell death with kinetics comparable to human prostate cancer radiotherapy. Secondly, the injection of Hoechst 33342 or fluorescent-dextrans showed an increased tumor perfusion within 14 days in irradiated tumors, which was correlated with a clear reduction of hypoxia. Improved perfusion and decreased hypoxia were not explained by increased blood vessel density, size or network morphology. However, a tumor vascular maturation defined by perivascular desmin+/SMA+ cells coverage was clearly observed along with an increase in endothelial, zonula occludens (ZO)-1 positive, intercellular junctions. Our results show that, in addition to tumor cell killing, vascular maturation plays an uncovered role in tumor reoxygenation during fractionated radiation therapy.
authors.affiliation: Inserm, UMR892, Nantes, France ; Université de Nantes, Nantes, France ; CNRS, UMR6299, Nantes, France.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Potiron
authors.affiliation: Inserm, UMR892, Nantes, France ; Université de Nantes, Nantes, France ; CNRS, UMR6299, Nantes, France.
authors.forename: Rym
authors.initials: R
authors.lastname: Abderrahmani
authors.affiliation: Inserm, UMR892, Nantes, France ; Université de Nantes, Nantes, France ; CNRS, UMR6299, Nantes, France ; Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, Saint-Herblain, France.
authors.forename: Karen
authors.initials: K
authors.lastname: Clément-Colmou
authors.affiliation: Plate-forme in vivo, Cancéropôle Grand-Ouest, Nantes, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Marionneau-Lambot
authors.affiliation: Plate-forme in vivo, Cancéropôle Grand-Ouest, Nantes, France.
authors.forename: Thibauld
authors.initials: T
authors.lastname: Oullier
authors.affiliation: Inserm, UMR892, Nantes, France ; Université de Nantes, Nantes, France ; CNRS, UMR6299, Nantes, France ; Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, Saint-Herblain, France.
authors.forename: François
authors.initials: F
authors.lastname: Paris
authors.affiliation: Inserm, UMR892, Nantes, France ; Université de Nantes, Nantes, France ; CNRS, UMR6299, Nantes, France ; Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, Saint-Herblain, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Supiot
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D015687:Cell Hypoxia / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008297:Male; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000532:radiotherapy*; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000532:radiotherapy
chemical_list: D014408:Biomarkers, Tumor