Inhibiting platelet-derived growth factor beta reduces Ewing's sarcoma growth and metastasis in a novel orthotopic human xenograft model.
BACKGROUND
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.


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 beta (PDGFR-beta) is highly expressed in ES. Hypothesizing that PDGFR-beta expression is indicative of a specific role for this receptor protein in ES progression, the effect of PDGFR-beta inhibition on ES growth and metastasis was assessed in this novel orthotopic ES model.


RESULTS
Silencing PDGFR-beta reduced spontaneous growth and metastasis in ES.


CONCLUSIONS
Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.
Wang
Yong Xin
YX
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston TX 77030, USA. ahjordan@mdanderson.org
Mandal
Deendayal
D
Wang
Suizhau
S
Hughes
Dennis
D
Pollock
Raphael E
RE
Lev
Dina
D
Kleinerman
Eugenie
E
Hayes-Jordan
Andrea
A
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034622:RNA Interference; D016372:RNA, Antisense / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D023041:Xenograft Model Antitumor Assays
D016372:RNA, Antisense; D020797:Receptor, Platelet-Derived Growth Factor beta