van der Schaft, DW and Hillen, F and Pauwels, P and Kirschmann, DA and Castermans, K and Egbrink, MG and Tran, MG and Sciot, R and Hauben, E and Hogendoorn, PC and Delattre, O and Maxwell, PH and Hendrix, MJ and Griffioen, AW (2005) Tumor cell plasticity in Ewing sarcoma, an alternative circulatory system stimulated by hypoxia. Cancer Res , 65 (24) 11520 - 11528. 10.1158/0008-5472.CAN-05-2468.
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A striking feature of Ewing sarcoma is the presence of blood lakes lined by tumor cells. The significance of these structures, if any, is unknown. Here, we report that the extent of blood lakes correlates with poor clinical outcomes, whereas variables of angiogenesis do not. We also show that Ewing sarcoma cells form vessel-like tubes in vitro and express genes associated with vasculogenic mimicry. In tumor models, we show that there is blood flow through the blood lakes, suggesting that these structures in Ewing sarcoma contribute to the circulation. Furthermore, we present evidence that reduced oxygen tension may be instrumental in tube formation by plastic tumor cells. The abundant presence of these vasculogenic structures, in contrast to other tumor types, makes Ewing sarcoma the ideal model system to study these phenomena. The results suggest that optimal tumor treatment may require targeting of these structures in combination with prevention of angiogenesis.
|Title:||Tumor cell plasticity in Ewing sarcoma, an alternative circulatory system stimulated by hypoxia.|
|Keywords:||Adolescent, Adult, Animals, Bone Neoplasms, Cell Hypoxia, Child, Child, Preschool, Collagen, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Mice, Mice, Nude, Microcirculation, Middle Aged, Neovascularization, Pathologic, Phenotype, Sarcoma, Ewing, Tumor Cells, Cultured|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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