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Commun Biol ; 3(1): 579, 2020 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-33067561

RESUMEN

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.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Meduloblastoma/genética , Meduloblastoma/patología , Factor C de Crecimiento Endotelial Vascular/genética , Animales , Biomarcadores de Tumor , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal/genética , Xenoinjertos , Humanos , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Meduloblastoma/metabolismo , Meduloblastoma/mortalidad , Ratones , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Pronóstico , Factor C de Crecimiento Endotelial Vascular/metabolismo
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