Adenoviral-mediated gene transfer of ectodysplasin-A2 results in induction of apoptosis and cell-cycle arrest in osteosarcoma cell lines.

Abstract

The extremely poor prognosis of patients with metastatic osteosarcoma indicates the need for novel therapeutic approaches. Ectodysplasin-A2 (EDA-A2) is a recently isolated member of the tumor necrosis factor superfamily that binds to X-linked ectodermal dysplasia receptor (XEDAR). In this report, we have analyzed the biological activity of EDA-A2 against osteosarcoma-derived cell lines. We report that XEDAR is expressed in cell lines derived from osteosarcoma and adenoviral-mediated expression of EDA-A2 in these cells results in the induction of apoptosis via caspase activation and cell-cycle arrest in the G(0)/G(1) phase. Treatment with EDA-A2 also upregulates the expression of alkaline phosphatase, a marker of osteogenic differentiation, in a caspase-dependent fashion. Collectively, our results suggest that EDA-A2 may be a promising agent for the gene therapy of osteosarcoma.

• Authors: B Chang, V Punj, M Shindo, P M Chaudhary
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 14 Issue 11 Pg. 927-33 (Nov 2007) ISSN: 0929-1903 [Print] England
• PMID: 17693991 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• EDA2R protein, human
• Ectodysplasins
• Xedar Receptor
• Caspases

Topics

• Adenoviridae (genetics)
• Apoptosis
• Bone Neoplasms (therapy)
• Caspases (metabolism)
• Cell Cycle
• Cell Line, Tumor
• Cell Proliferation
• Ectodysplasins (genetics)
• Gene Transfer Techniques
• Genetic Therapy (methods)
• Humans
• Osteosarcoma (therapy)
• Xedar Receptor (metabolism)