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VEGFC negatively regulates the growth and aggressiveness of medulloblastoma cells

Abstract : Medulloblastoma (MB), the most common brain pediatric tumor, is a pathology composed of four molecular subgroups. Despite a multimodal treatment, 30% of the patients eventually relapse, with the fatal appearance of metastases within 5 years. The major actors of meta-static dissemination are the lymphatic vessel growth factor, VEGFC, and its receptors/co-receptors. Here, we show that VEGFC is inversely correlated to cell aggressiveness. Indeed, VEGFC decreases MB cell proliferation and migration, and their ability to form pseudo-vessel in vitro. Irradiation resistant-cells, which present high levels of VEGFC, lose the ability to migrate and to form vessel-like structures. Thus, irradiation reduces MB cell aggressiveness via a VEGFC-dependent process. Cells intrinsically or ectopically overexpressing VEGFC and irradiation-resistant cells form smaller experimental tumors in nude mice. Opposite to the common dogma, our results give strong arguments in favor of VEGFC as a negative regulator of MB growth.
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Submitted on : Tuesday, October 20, 2020 - 3:39:15 PM
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Manon Penco-Campillo, Yannick Comoglio, Álvaro Javier Feliz Morel, Rita Hanna, Jérôme Durivault, et al.. VEGFC negatively regulates the growth and aggressiveness of medulloblastoma cells. Communications Biology, Nature Publishing Group, 2020, 3 (1), pp.579. ⟨10.1038/s42003-020-01306-4⟩. ⟨hal-02972715⟩

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