title: Tumor cell plasticity in Ewing sarcoma, an alternative circulatory system stimulated by hypoxia.
abstract: 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.
authors.affiliation: Angiogenesis Laboratory, Research Institute for Growth and Development, Department of Pathology, Maastricht University and University Hospital Maastricht, the Netherlands.
authors.forename: Daisy W J
authors.initials: DW
authors.lastname: van der Schaft
authors.forename: Femke
authors.initials: F
authors.lastname: Hillen
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Kirschmann
authors.forename: Karolien
authors.initials: K
authors.lastname: Castermans
authors.forename: Mirjam G A Oude
authors.initials: MG
authors.lastname: Egbrink
authors.forename: Maxine G B
authors.initials: MG
authors.lastname: Tran
authors.forename: Rafael
authors.initials: R
authors.lastname: Sciot
authors.forename: Esther
authors.initials: E
authors.lastname: Hauben
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Maxwell
authors.forename: Mary J C
authors.initials: MJ
authors.lastname: Hendrix
authors.forename: Arjan W
authors.initials: AW
authors.lastname: Griffioen
mesh_terms: 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
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003094:Collagen