Hypoxia-induced dedifferentiation in neuroblastoma cells.

Hypoxia in solid tumors is associated with aggressive behavior and poor outcome. We recently discovered that hypoxia alters the expression of differentiation marker genes in neuroblastoma cells, in that the tumor cells adjust to the hypoxic environment by down-regulating genes associated with a neuronal and upregulating genes associated with a neural crest-like phenotype. As there is a correlation in neuroblastoma between low stage of differentiation and high (aggressive) clinical stage, we propose that dedifferentiation of neuroblastoma cells in hypoxic tumor regions contribute to the malignancy of the tumor.