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. 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 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. CONCLUSION: Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.
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. 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 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. CONCLUSION: Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.
Authors: Sung-Hyeok Hong; Jason U Tilan; Susana Galli; Rachel Acree; Katherine Connors; Akanksha Mahajan; Larissa Wietlisbach; Taylor Polk; Ewa Izycka-Swieszewska; Yi-Chien Lee; Luciane R Cavalli; Olga C Rodriguez; Chris Albanese; Joanna B Kitlinska Journal: J Vis Exp Date: 2016-12-09 Impact factor: 1.355
Authors: J K Simmons; B E Hildreth; W Supsavhad; S M Elshafae; B B Hassan; W P Dirksen; R E Toribio; T J Rosol Journal: Vet Pathol Date: 2015-05-28 Impact factor: 2.221
Authors: Britta Vormoor; Henrike K Knizia; Michael A Batey; Gilberto S Almeida; Ian Wilson; Petra Dildey; Abhishek Sharma; Helen Blair; I Geoff Hide; Olaf Heidenreich; Josef Vormoor; Ross J Maxwell; Chris M Bacon Journal: PLoS One Date: 2014-01-07 Impact factor: 3.240