RT Journal Article
SR Electronic
T1 Inhibiting Platelet-derived Growth Factor β Reduces Ewing's Sarcoma Growth and Metastasis in a Novel Orthotopic Human Xenograft Model
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 903
OP 909
VO 23
IS 6
A1 WANG, YONG XIN
A1 MANDAL, DEENDAYAL
A1 WANG, SUIZHAU
A1 HUGHES, DENNIS
A1 POLLOCK, RAPHAEL E.
A1 LEV, DINA
A1 KLEINERMAN, EUGENIE
A1 HAYES-JORDAN, ANDREA
YR 2009
UL http://iv.iiarjournals.org/content/23/6/903.abstract
AB Backgound: Despite aggressive therapy, Ewing's sarcoma (ES) patients have a poor five-year overall survival of only 20-40%. Pulmonary metastasis is the most common form of demise in these patients. The pathogenesis of pulmonary metastasis is poorly understood and few orthotopic models exist that allow study of spontaneous pulmonary metastasis in ES. Materials and Methods: We have developed a novel orthotopic xenograft model in which spontaneous pulmonary metastases develop. While the underlying biology of ES is incompletely understood, in addition to the EWS-FLI-1 mutation, it is known that platelet-derived growth factor receptor β (PDGFR-β) is highly expressed in ES. Hypothesizing that PDGFR-β expression is indicative of a specific role for this receptor protein in ES progression, the effect of PDGFR-β inhibition on ES growth and metastasis was assessed in this novel orthotopic ES model. Results: Silencing PDGFR-β reduced spontaneous growth and metastasis in ES. Conclusion: Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.