VEGFC negatively regulates the growth and aggressiveness of medulloblastoma cells
Manon Penco-Campillo, Yannick Comoglio, Álvaro Javier Feliz Morel, Rita Hanna, Jérôme Durivault, Magalie Leloire, Bastien Mejias, Marina Pagnuzzi, Amandine Morot, Fanny Burel‐Vandenbos, Matthew Selby, Daniel Williamson, Steven C. Clifford, Audrey Claren, J. Doyen, Vincent Picco, Sonia Martial, Gilles Pagès
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 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.