Abstract
Solid tumors are poorly oxygenated due to insufficient blood supply. Despite that the majority of cells in solid tumor are hypoxic, they both survive and grow under hypoxic conditions. Thus, tumor cells have the ability to adapt to hypoxia, which highly affects the phenotype as well as behavior of distinct cells and the tumor as a whole. Instrumental in this adaptation process, which also occurs in non-transformed cells, are the hypoxia inducible transcription factors HIF-1 and HIF-2 and their oxygen sensitive alpha subunits. In neuroblastoma, a tumor derived from sympathetic nervous system precursor cells, HIF signaling is particularly important as HIF-2α is a marker of unfavorable disease and as it turns out, also of immature neural crest-like, neuroblastoma cells, which is in line with the temporal embryonal expression of HIF-2α during discrete periods of sympathetic nervous system development. Here we review the general mechanisms by which tumor cells adapt to hypoxia and in particular, the role of HIF-2α in aggressive neuroblastoma disease, which primarily is not linked to hypoxic stabilization of HIF-2α, but rather appears to be an inherent property of immature neuroblastoma cells.
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Acknowledgements
This work was supported by the Swedish Cancer Society, the Children’s Cancer Foundation of Sweden, the Swedish Research Council, the SSF Strategic Center for Translational Cancer Research – CREATE Health, BioCARE, a Strategic Research Program at Lund University, Gunnar Nilsson’s Cancer Foundation and the research funds of Malmö University Hospital.
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Fredlund, E., Pietras, A., Jögi, A., Påhlman, S. (2012). Neuroblastoma: Role of Hypoxia and Hypoxia Inducible Factors in Tumor Progression. In: Hayat, M. (eds) Neuroblastoma. Pediatric Cancer, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2418-1_13
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DOI: https://doi.org/10.1007/978-94-007-2418-1_13
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