Tumor cell plasticity in Ewing sarcoma, an alternative circulatory system stimulated by hypoxia

Daisy W.J. Van Der Schaft, Femke Hillen, Patrick Pauwels, Dawn A. Kirschmann, Karolien Castermans, Mirjam G.A. Oude Egbrink, Maxine G.B. Tran, Rafael Sciot, Esther Hauben, Pancras C.W. Hogendoorn, Olivier Delattre, Patrick H. Maxwell, Mary J.C. Hendrix, Arjan W. Griffioen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

183 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)11520-11528
Number of pages9
JournalCancer Research
Issue number24
StatePublished - Dec 15 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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