Influence of Radiotherapy Fractionation Schedule on the Tumor Vascular Microenvironment in Prostate and Lung Cancer Models

Cancers

Vincent Potiron¹  Manon Pietri¹  Maëva Guillonneau¹  Sophie Chiavassa¹  Stéphane Supiot¹  Grégory Delpon¹  Karen Clément-Colmou¹  Emmanuel Jouglar¹  François Paris¹ 

[1] Centre de Recherche en Cancérologie Immunologie Nantes Angers (CRCINA), Institut National de Santé et de la Recherche Médicale (INSERM) UMR U1232, Centre National de la Recherche Scientifique (CNRS) ERL 6001, Université de Nantes, 44007 Nantes, France;

关键词: radiotherapy;    fractionation;    microenvironment;    vasculature;    hypoxia;    stereotactic radiotherapy;   

DOI  :  10.3390/cancers12010121

来源: DOAJ

【 摘 要 】

Background. The tumor vasculature acts as an interface for the primary tumor. It regulates oxygenation, nutrient delivery, and treatment efficacy including radiotherapy. The response of the tumor vasculature to different radiation doses has been disparately reported. Whereas high single doses can induce endothelial cell death, improved vascular functionality has also been described in a various dose range, and few attempts have been made to reconcile these findings. Therefore, we aimed at comparing the effects of different radiation fractionation regimens on the tumor vascular microenvironment. Methods: Lewis lung and prostate PC3 carcinoma-derived tumors were irradiated with regimens of 10 × 2 Gy, 6 × 4 Gy, 3 × 8 Gy or 2 × 12 Gy fractions. The tumor vasculature phenotype and function was evaluated by immunohistochemistry for endothelial cells (CD31), pericytes (desmin, α-SMA), hypoxia (pimonidazole) and perfusion (Hoechst 33342). Results: Radiotherapy increased vascular coverage similarly in all fractionation regimens in both models. Vessel density appeared unaffected. In PC3 tumors, hypoxia was decreased and perfusion was enhanced in proportion with the dose per fraction. In LLC tumors, no functional changes were observed at t = 15 days, but increased perfusion was noticed earlier (t = 9−11 days). Conclusion: The vascular microenvironment response of prostate and lung cancers to radiotherapy consists of both tumor/dose-independent vascular maturation and tumor-dependent functional parameters.

【 授权许可】

Unknown