Adenoviral-mediated gene transfer of ectodysplasin-A2 results in induction of apoptosis and cell-cycle arrest in osteosarcoma cell lines.
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.
Chang
B
B
1Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA.
Punj
V
V
Shindo
M
M
Chaudhary
P M
PM
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D001859:Bone Neoplasms / Q000628:therapy*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053331:Ectodysplasins / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D012516:Osteosarcoma / Q000628:therapy*; D053340:Xedar Receptor / Q000378:metabolism
C506011:EDA2R protein, human; D053331:Ectodysplasins; D053340:Xedar Receptor; D020169:Caspases