Abstract
Previously, we observed expression of the homeobox transcription factor Prox1 in neuroectodermal embryonic tissues. Besides essential functions during embryonic development, Prox1 has been implicated in both progression and suppression of malignancies. Here, we show that Prox1 is expressed in embryonic sympathetic trunk ganglia of avian and murine embryos. Prox1 protein is localized in the nucleus of neurofilament-positive sympathetic neurons. Sympathetic progenitors represent the cell of origin of neuroblastoma (NB), the most frequent solid extracranial malignancy of children. NB may progress to life-threatening stage 4, or regress spontaneously in the special stage 4s. By qRT-PCR, we show that Prox1 is expressed at low levels in 24 human NB cell lines compared with human lymphatic endothelial cells (LECs), whereas equal immunostaining of nuclei can be seen in embryonic LECs and sympathetic neurons. In NB stages 1, 2, 3, and 4, we observed almost equal expression levels, but significantly higher amounts in stage 4s NB. By immunohistochemistry, we found variable amounts of Prox1 protein in nuclei of NB cells, showing intra and interindividual differences. Because stage 4s NB are susceptible to postnatal apoptosis, we assume that high Prox1 levels are critical for their behavior.
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Abbreviations
- ED:
-
embryonic day
- ISH:
-
in situ hybridization
- LEC:
-
lymphatic endothelial cell(s)
- NB:
-
neuroblastoma
- PFA:
-
paraformaldehyde
- PCNA:
-
proliferating cell nuclear antigene
- Prox1:
-
prospero-related homeobox transcription factor-1
- TH:
-
tyrosine hydroxylase
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Acknowledgements
We thank Mrs. S. Schwoch, Mrs. Ch. Zelent, Mr. B. Manshausen, Mr. M. Winkler, and Mr. F. Ludewig for their excellent technical assistance; and Drs. F. Berthold, B. Hero, and J. Theissen (German Neuroblastoma Studies Group, Children's Hospital University Cologne, Cologne, Germany) for providing tumor samples and data.
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Becker, J., Wang, B., Pavlakovic, H. et al. Homeobox Transcription Factor Prox1 in Sympathetic Ganglia of Vertebrate Embryos: Correlation With Human Stage 4s Neuroblastoma. Pediatr Res 68, 112–117 (2010). https://doi.org/10.1203/PDR.0b013e3181e5bc0f
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DOI: https://doi.org/10.1203/PDR.0b013e3181e5bc0f
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