Recombinant Semliki forest virus infects and kills human prostate cancer cell lines and prostatic duct epithelial cells ex vivo.
Semliki Forest Virus (SFV) is a broad host range RNA virus capable of high-level recombinant protein expression and apoptosis induction in many cell types. We have successfully used a recombinant, replication deficient SFV vector to express the LacZ marker gene product in seven human prostate cell lines, as well as in human prostate tissue explants. Flow cytometry revealed that 40-60% of PPC-1 prostate cancer cells died 24-72 h after infection with SFV-LacZ virus. Most human prostate cancer cell lines expressed high levels of recombinant protein. Infection of human prostate tissue ex vivo led to similarly high expression levels but the recombinant beta-galactosidase was confined to duct epithelial cells. Infection of cell and tissue cultures resulted in detachment of adherent cells from the culture surface and detachment of epithelial cells from the basement membrane of tissue. Our results indicate that SFV may be useful in targeting recombinant protein expression and apoptosis to prostatic duct epithelial cells.
Hardy
P A
PA
Medical Oncology B171, School of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Mazzini
M J
MJ
Schweitzer
C
C
Lundstrom
K
K
Glode
L M
LM
D017209:Apoptosis; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000821:virology; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007763:Lac Operon; D008297:Male; D011467:Prostate / Q000166:cytology* / Q000821:virology; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000821:virology; D011995:Recombination, Genetic; D012672:Semliki forest virus / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured