Inhibition of Neuroblastoma Progression by Targeting Lymphangiogenesis: Role of an Endogenous Soluble Splice-Variant of VEGFR-2

摘要: The endogenous-soluble-vascular-endothelial-growth-factor-receptor-2 (esVEGFR-2) is a novel member of the VEGFR-family. It generated from VEGFR-2 gene by alternative splicing and was shown to bind VEGF-C with high affinity, therefore acting as an endogenous inhibitor lymphangiogenesis. Still little known about its functions in development disease. We explored distribution patterns esVEGFR-2 human embryonic tissues found it expressed many organs structures throughout developing organism. Most interestingly, sympathetic ganglia adrenal medulla were positive for inhibitor, too. Neuroblastoma tumor, progenitor cells neural crest, which normal form nervous system well medulla. Immunohistology revealed that neuroblastoma differentiating type histopathology differentiated tumors ganglioneuroblastoma type, regularly, whereas highly malignant undifferentiated phenotype could be rarely detected. All-trans-retinoic acid (ATRA) crucial compound differentiation processes. has also been induce vitro, part clinical regimen treatment. treated ATRA showed increased expression esVEGFR-2, suggesting may indicate vice versa. Real-time RT-PCR analyses INSS stage 1 2 neuroblastomas express higher amounts transcripts than 3 4 tumors. Intriguingly, down-regulation inversely correlates lymph-node involvement metastasis formation.