Quantification and characterization of the bystander effect in prostate cancer cells following adenovirus-mediated FasL expression

Academic Article


  • Inducing Fas-mediated apoptosis in prostate cancer (PCa) is a promising new therapeutic approach with the potential to overcome delivery issues currently problematic in cancer gene therapy. We have previously demonstrated that a Fas Ligand (FasL) expressing adenovirus (AdGFPFasLTET) was able to induce Fas-mediated apoptosis in a panel of PCa cell lines regardless of their Fas-sensitivity as determined by the agonistic Fas antibody CH-11. We now report that AdGFPFasLTET-infected cells produce apoptotic bodies and cellular debris that continues to elicit FasL-mediated bystander killing in uninfected neighboring cells. Using light microscopy, we demonstrate that AdGFPFasLTET-infected cells release apoptotic bodies and cellular debris into the local environment and that this material will induce bystander killing in Jurkat, PPC-1, and PC-3 target cells, but not in DU145 and K-562 cells. The bystander killing mechanism is mediated through Fas/FasL interaction because it is significantly inhibited if target cells are pretreated with the pan spectrum caspase inhibitor Z-VAD-FMK or the Fas neutralizing antibody ZB-4. Coincubation of PPC-1 target cells with apoptotic bodies and cellular debris (effector material) induce nearly complete target cell killing at a ratio of 1:1 target to effector. Collectively, these data indicate that AdGFPFasLTET-infected PCa cells release apoptotic and cellular debris capable of inducing bystander killing in PCa and supports the development of FasL as a gene therapy agent.
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    Digital Object Identifier (doi)

    Author List

  • Hyer ML; Sudarshan S; Schwartz DA; Hannun Y; Dong JY; Norris JS
  • Start Page

  • 330
  • End Page

  • 339
  • Volume

  • 10
  • Issue

  • 4