Unexpected Effects of Photontherapy and Protontherapy on VEGFC Production and Tumor Aggressiveness in Different Medulloblastoma Subgroups - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2019

Unexpected Effects of Photontherapy and Protontherapy on VEGFC Production and Tumor Aggressiveness in Different Medulloblastoma Subgroups

Alvaro Javier
  • Fonction : Auteur
Feliz Morel
  • Fonction : Auteur
Rita Hanna
  • Fonction : Auteur
Magalie Leloire
  • Fonction : Auteur
Marina Pagnuzzi
  • Fonction : Auteur
Vincent Picco
Audrey Claren
  • Fonction : Auteur
Jérôme Doyen
  • Fonction : Auteur
Gilles Pagès Ab
  • Fonction : Auteur
Sonia Martial

Résumé

Medulloblastoma (MB) is the most common malignant cerebellar pediatric tumor. MB is a heterogeneous pathology composed of four molecular subgroups, with variable prognoses depending on the subgroup. MB treatment includes surgical resection of the tumor, craniospinal X-ray irradiation (the reference treatment of most cancers) and adjuvant chemotherapy. Despite this treatment, 30% of the patients relapse. Their progression is marked by the fatal appearance of metastases within 5 years. According to the current dogma, the major actors of metastatic dissemination are the lymphatic vessel growth factor, VEGFC, and its receptor, VEGFR3, in most cancers. Protontherapy, which allows higher precision of tumor targeting while reducing side effects and radio-induced cancers, is now emerging as an alternative treatment of MB. In this work, we meant to demonstrate the differential biological effects of protontherapy and photontherapy on MB, as a model of both brain and pediatric tumors. We repeatedly irradiated MB cell lines by high doses (8 Gy) of X-rays, low-energy protons or high-energy protons (Proteus® One equipment, IBA, Belgium), thus generating resistant cells for each form of irradiation. We measured the production of VEGFA (angiogenesis), VEGFC (as a read-out of lymphangiogenesis programming), and ELR+CXCL cytokines (inflammation). We also determined the aggressiveness of the cells by proliferation, migration, and pseudo-vessel formation assays. Finally, we measured the epithelial-to-mesenchymal transition status of the cells and the apparent stemness of the cells after irradiation. We demonstrated that X-ray resistant cells presented an increase in VEGFC production, thus pleading for a cell programming in favor of the generation of new lymphatic vessels. Unexpectedly, however, these cells showed lower aggressiveness than their naïve counterparts. Moreover, we demonstrated that, opposite to the admitted higher effect of protontherapy over photontherapy (EBR = 1.1), proton beams were less harmful to MB cells than photon beams, when these cells were irradiated in the same conditions as patients. Hence, our results present striking new evidence that i) VEGFC is a negative regulator of irradiation-induced MB aggressiveness; ii) opposite to the common dogma, proton irradiation reduces irradiation-induced damage to MB cells.
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Dates et versions

hal-02382818 , version 1 (04-12-2019)

Identifiants

  • HAL Id : hal-02382818 , version 1

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Yannick Comoglio, Alvaro Javier, Feliz Morel, Rita Hanna, Magalie Leloire, et al.. Unexpected Effects of Photontherapy and Protontherapy on VEGFC Production and Tumor Aggressiveness in Different Medulloblastoma Subgroups. 3rd ESM-EVBO Conference, Apr 2019, MAASTRICHT, Netherlands. ⟨hal-02382818⟩
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