Tumor cell plasticity in Ewing sarcoma, an alternative circulatory system stimulated by hypoxia.
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.
van der Schaft
Daisy W J
DW
Angiogenesis Laboratory, Research Institute for Growth and Development, Department of Pathology, Maastricht University and University Hospital Maastricht, the Netherlands.
Hillen
Femke
F
Pauwels
Patrick
P
Kirschmann
Dawn A
DA
Castermans
Karolien
K
Egbrink
Mirjam G A Oude
MG
Tran
Maxine G B
MG
Sciot
Rafael
R
Hauben
Esther
E
Hogendoorn
Pancras C W
PC
Delattre
Olivier
O
Maxwell
Patrick H
PH
Hendrix
Mary J C
MJ
Griffioen
Arjan W
AW
D000293:Adolescent; D000328:Adult; D000818:Animals; D001859:Bone Neoplasms / Q000098:blood supply / Q000503:physiopathology; D015687:Cell Hypoxia; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation / Q000473:pathology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010641:Phenotype; D012512:Sarcoma, Ewing / Q000098:blood supply* / Q000503:physiopathology*; D014407:Tumor Cells, Cultured / Q000637:transplantation
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003094:Collagen