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VEGFC negatively regulates the growth and aggressiveness of medulloblastoma cells

Lookup NU author(s): Professor Steven CliffordORCiD

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Abstract

© 2020, The Author(s).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 metastatic 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.


Publication metadata

Author(s): Penco-Campillo M, Comoglio Y, Feliz Morel AJ, Hanna R, Durivault J, Leloire M, Mejias B, Pagnuzzi M, Morot A, Burel-Vandenbos F, Selby M, Williamson D, Clifford SC, Claren A, Doyen J, Picco V, Martial S, Pages G

Publication type: Article

Publication status: Published

Journal: Communications Biology

Year: 2020

Volume: 3

Issue: 1

Online publication date: 16/10/2020

Acceptance date: 17/09/2020

ISSN (electronic): 2399-3642

Publisher: Nature Research

URL: https://doi.org/10.1038/s42003-020-01306-4

DOI: 10.1038/s42003-020-01306-4

PubMed id: 33067561


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