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The lymphangiogenesis inhibitor esVEGFR-2 in human embryos: expression in sympatho-adrenal tissues and differentiation-induced up-regulation in neuroblastoma

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dc.contributor.authorBecker, Jürgen
dc.contributor.authorFröhlich, Johanna
dc.contributor.authorHansen, Jan
dc.contributor.authorZelent, Christina
dc.contributor.authorPerske, Christina
dc.contributor.authorWilting, Jörg
dc.date.accessioned2017-03-13T15:20:25Z
dc.date.available2017-03-13T15:20:25Z
dc.date.issued2012
dc.description.abstractTumour-induced hem- and lymph-angiogenesis are frequently associated with tumour progression. Vascular Endothelial Growth Factor-C (VEGF-C) is a potent inducer of lymphangiogenesis, while the endogenous soluble splice-variant of VEGF receptor-2, esVEGFR-2, acts as a natural inhibitor. Previously we have shown down-regulation of esVEGFR-2 mRNA in progressed stages of neuro-blastoma (NB), a tumour derived from sympatho-adrenal precursor cells. Here we studied the immunolocalization of esVEGFR-2 in human embryos, infantile adrenal gland and primary NB. We also quantified esVEGFR-2 mRNA in NB cell lines after differentiation-induction by all-trans retinoic acid (ATRA). By immunoperoxidase staining we observed expression of esVEGFR-2 in both the sympathetic trunk and the adrenal medulla. Additionally, esVEGFR-2 was found in spinal ganglia, floor plate of the neural tube, choroid plexus, notochord, arterial endothelium, skeletal muscle, epidermis and gut epithelium. Developing and circulating leukocytes showed the strongest signal. In NB, esVEGFR-2 was considerably stronger in differentiating low grade tumours with neuronal phenotype than in undifferentiated lesions. Differentiation-induction of the NB cell line SMS-Kan with 5-10 µM ATRA resulted in a significant increase of esVEGFR-2 mRNA after 6, 9 and 12 days. We show that esVEGFR-2 is widely expressed in embryonic tissues. Especially, the adrenal medulla and circulating leukocytes seem to be potent inhibitors of lymphangiogenesis. We provide additional evidence for a role of esVEGFR-2 in NB. Thereby, high levels of esVEGFR-2 correlate with a more differentiated phenotype, and may inhibit tumour progression by inhibition of lymphangiogenesis.es
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dc.format.extent13es
dc.identifier.citationHistology and Histopatholy, Volume 27, number 6 (June), 2012
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/52448
dc.languageenges
dc.publisherF. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología.es
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.subjectMetastasises
dc.subjectAdrenal medullaes
dc.subject.otherCDU::5 - Ciencias puras y naturales::57 - Biologíaes
dc.titleThe lymphangiogenesis inhibitor esVEGFR-2 in human embryos: expression in sympatho-adrenal tissues and differentiation-induced up-regulation in neuroblastomaes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.27, nº 6 (2012)