Abstract
Tumor cells expressing the herpes simplex virus thymidine kinase (HSV-TK) gene are sensitive to the drug ganciclovir (GCV). We demonstrate here that HSV-TK-positive cells exposed to GCV were lethal to HSV-TK-negative cells as a result of a “bystander effect” HSV-TK-negative cells were killed in vitro when the population of cultured cells contained only 10% HSV-TK-positive cells. The mechanism of this “bystander effect” on HSV-TK-negative cells appeared to be related to the process of apoptotic cell death when HSV-TK-positive cells were exposed to GCV. Flow cytometric and electron microscopic analyses suggested that apoptotic vesicles generated from the dying gene-modified cells were phagocytized by nearby, unmodified tumor cells. Prevention of apoptotic vesicle transfer prevented the bystander effect.
Original language | English (US) |
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Pages (from-to) | 5274-5283 |
Number of pages | 10 |
Journal | Cancer Research |
Volume | 53 |
Issue number | 21 |
State | Published - Nov 1993 |
Externally published | Yes |
ASJC Scopus subject areas
- Oncology
- Cancer Research