Sensitization of human keratinocytes to killing by parvovirus H-1 takes place during their malignant transformation but does not require them to be tumorigenic.
To investigate the antineoplastic activity of parvoviruses, proliferating normal human epidermal cells and a series of established keratinocyte cell lines derived from squamous cell carcinomas or transformed in vitro, were compared for the outcome of H-1 virus infection. All established keratinocyte cell lines were more sensitive to killing by H-1 virus than normal epidermal cells, although to varying extents. Using a step-wise procedure for malignant transformation in vitro, we found that sensitization of transformed epidermal cells to H-1 virus can be dissociated from the acquisition of a tumorigenic phenotype. Thus, spontaneously- or SV40-immortalized human keratinocytes were moderately and highly sensitive to H-1 virus, respectively, and could be made tumorigenic by Harvey-ras oncogene transfection without a major change in their susceptibility to the virus. The capacity of human keratinocytes for replicating and expressing H-1 virus DNA appears to be a revealer of cellular alterations that take place in at least some pathways to malignant transformation but that may be insufficient to confer a tumorigenic potential.
Chen
Y Q
YQ
Laboratory of Biophysics and Radiobiology, Université Libre de Bruxelles, Belgium.
Tuynder
M C
MC
Cornelis
J J
JJ
Boukamp
P
P
Fusenig
N E
NE
Rommelaere
J
J
D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000382:microbiology* / Q000503:physiopathology; D002472:Cell Transformation, Viral; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000096:biosynthesis; D004817:Epidermis / Q000382:microbiology*; D006801:Humans; D007633:Keratins; D010321:Parvoviridae / Q000472:pathogenicity*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D004279:DNA, Viral; D007633:Keratins