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.
Written by:
Potiron VA1, Abderrahmani R1, Clément-Colmou K2, Marionneau-Lambot S3, Oullier T3, Paris F2, Supiot S2 Are you the author?
1Inserm, UMR892, Nantes, France ; Université de Nantes, Nantes, France ; CNRS, UMR6299, Nantes, France. 2Inserm, 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. 3Plate-forme in vivo, Cancéropôle Grand-Ouest, Nantes, France.
Reference: PLoS One. 2013 Dec 31;8(12):e84076. eCollection 2013
doi: 10.1371/journal.pone.0084076
PubMed Abstract
PMID: 24391887
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