Ewing sarcoma family of tumors express adenovirus receptors and are susceptible to adenovirus-mediated oncolysis.
OBJECTIVE
Attenuated viruses derived from adenoviruses (Ad) that kill tumor cells (oncolysis) are currently in clinical trials for selected cancers. Some cancers have proven resistant to Ad infection due to low expression of viral receptors. The authors sought to determine whether members of the Ewing sarcoma family of tumors (ESFTs) express Ad receptors and are sensitive to Ad-mediated oncolysis.


METHODS
Using flow cytometry, the authors tested a panel of cell lines derived from ESFTs for expression of both the Ad receptor, coxsackie-adenovirus receptor (CAR), and the cellular mediator of Ad uptake, alpha(v)-integrins, as well as for Ad-mediated gene transduction. Cell survival assays were used to assess the sensitivity to Ad-mediated oncolysis. Immunohistochemistry was used to assess CAR expression in primary tumors. mRNA levels of CAR in cell lines and tumor samples were also queried from a cDNA expression database.


RESULTS
The ESFT cell lines expressed CAR and alpha(v)-integrins, showed high levels of gene transduction, and were highly sensitive to viral oncolysis. Primary tumor samples were positive for CAR expression by immunohistochemistry. Microarray analysis confirmed CAR expression in ESFT cell lines and tumors.


CONCLUSIONS
Ewing sarcoma cells express the Ad receptors and are sensitive to Ad oncolysis. Treatment of Ewing sarcoma using conditionally replicative adenoviruses should be explored.
D000256:Adenoviridae / Q000502:physiology*; D002470:Cell Survival; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000378:metabolism; D040081:Protein Array Analysis; D011991:Receptors, Virus / Q000378:metabolism*; D012512:Sarcoma, Ewing / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D039001:Integrin alpha Chains; D011991:Receptors, Virus; C085301:adenovirus receptor