VEGFC negatively regulates the growth and aggressiveness of medulloblastoma cells

Commun Biol. 2020 Oct 16;3(1):579. doi: 10.1038/s42003-020-01306-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Models, Animal
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic*
  • Heterografts
  • Humans
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Medulloblastoma / genetics*
  • Medulloblastoma / metabolism
  • Medulloblastoma / mortality
  • Medulloblastoma / pathology*
  • Mice
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Prognosis
  • Vascular Endothelial Growth Factor C / genetics*
  • Vascular Endothelial Growth Factor C / metabolism

Substances

  • Biomarkers, Tumor
  • VEGFC protein, human
  • Vascular Endothelial Growth Factor C