Oncolytic virotherapy for human bone and soft tissue sarcomas using live attenuated poliovirus

Int J Oncol. 2012 Sep;41(3):893-902. doi: 10.3892/ijo.2012.1514. Epub 2012 Jun 12.

Abstract

The poliovirus receptor CD155, is essential for poliovirus to infect and induce death in neural cells. Recently, CD155 has been shown to be selectively expressed on certain types of tumor cells originating from the neural crest, including malignant glioma and neuroblastoma. However, the expression pattern of CD155 in soft tissue sarcoma has not been examined. Therefore, we first examined CD155 expression in sarcoma cell lines, and found the expression of both CD155 mRNA and protein in 12 soft and bone tissue sarcoma cell lines. Furthermore, we examined the effect of live attenuated poliovirus (LAPV) on 6 bone and soft tissue sarcoma cell lines in vitro, and found that LAPV induced apoptosis by activating caspases 7 and 3 in all of these cell lines. Furthermore, in BALB/c nu/nu mice xenotransplanted with HT1080 fibrosarcoma cells, administration of live attenuated poliovirus caused growth suppression of the tumors. These results suggest that oncolytic therapy using a LAPV may represent a new option for the treatment of bone and soft tissue sarcomas.

MeSH terms

  • Animals
  • Apoptosis
  • Bone Neoplasms / therapy*
  • Caspase 3 / biosynthesis
  • Caspase 7 / biosynthesis
  • Cell Line, Tumor
  • Humans
  • Mice
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses* / pathogenicity
  • Osteosarcoma / therapy*
  • Poliovirus* / pathogenicity
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Virus / biosynthesis
  • Receptors, Virus / genetics*
  • Sarcoma / therapy*
  • Xenograft Model Antitumor Assays

Substances

  • RNA, Messenger
  • Receptors, Virus
  • poliovirus receptor
  • Caspase 3
  • Caspase 7