1. ¹Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA
2. ²Division of Hematology–Oncology, Department of Medicine, The Hillman Cancer Center, University of Pittsburgh, PA, USA
3. ³Department of Dermatology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan

Correspondence: Dr PM Chaudhary, Department of Medicine, University of Pittsburg, Hillman Cancer Center, 5117 Centre Avenue, Suite 1.19A, Pittsburgh, PA 15213-1863, USA. E-mail: chaudharypm@upmc.edu

⁴These authors have contributed equally to this work.

Received 6 January 2007; Revised 21 May 2007; Accepted 24 June 2007; Published online 10 August 2007.

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 G₀/G₁ 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.