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

Abstract

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: Yong Xin Wang, Deendayal Mandal, Suizhau Wang, Dennis Hughes, Raphael E Pollock, Dina Lev, Eugenie Kleinerman, Andrea Hayes-Jordan
• Journal: In vivo (Athens, Greece) (In Vivo) 2009 Nov-Dec Vol. 23 Issue 6 Pg. 903-9 ISSN: 0258-851X [Print] Greece
• PMID: 20023231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Antisense
• Receptor, Platelet-Derived Growth Factor beta

Topics

• Animals
• Bone Neoplasms (genetics, metabolism, pathology)
• Disease Progression
• Female
• Gene Knockdown Techniques
• Gene Silencing
• Humans
• Lung Neoplasms (genetics, metabolism, secondary)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• RNA Interference
• RNA, Antisense (genetics)
• Receptor, Platelet-Derived Growth Factor beta (genetics)
• Sarcoma, Ewing (genetics, metabolism, secondary)
• Xenograft Model Antitumor Assays