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Evidence for hypoxia-induced neuronal-to-chromaffin metaplasia in neuroblastoma

Hedborg, F; Ulleras, E; Grimelius, L; Wassberg, E; Maxwell, PH; Hero, B; ... Franklin, G; + view all (2003) Evidence for hypoxia-induced neuronal-to-chromaffin metaplasia in neuroblastoma. FASEB J , 17 (6) 598 - 609.

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Abstract

We present evidence that in neuroblastoma, a pediatric malignancy of embryonal sympathetic origin, hypoxia, underlies a phenotypic switch from a primitive neuronal to a chromaffin cell type. This conclusion is based on morphological and molecular data on 116 clinical tumors and is supported by data on the phenotypic effects of hypoxia on neuroblastoma cell lines when studied in monolayer culture and as tumor xenografts. In the clinical material, extensive chromaffin features were seen in regions of chronic tumor hypoxia. This was the exclusive form of intratumoral maturation of stroma-poor tumors and was also seen in stroma-rich tumors, either exclusively or in combination with ganglion-like cells. In neuroblastoma cell lines, hypoxia induced changes in gene expression associated with the chromaffin features observed in vivo. We therefore propose tumor hypoxia as a major cue determining phenotype in sympathetic tumors of neuroblastic origin. Because it appears to be reversible upon reoxygenation in monolayer culture, we suggest the term metaplasia for the phenomenon.

Type:Article
Title:Evidence for hypoxia-induced neuronal-to-chromaffin metaplasia in neuroblastoma
Keywords:angiogenesis, differentiation, sympathetic nervous system, insulin-like growth factor, vascular-endothelial growth factor, GROWTH-FACTOR-II, INDUCIBLE FACTOR 1-ALPHA, GENE-EXPRESSION, O-2 HOMEOSTASIS, NERVOUS-SYSTEM, TUMORS, CELLS, CANCER, DIFFERENTIATION, TRANSCRIPTION
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)

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