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CHEMOTHERAPY AGENT TRANSMITS DEATH SIGNAL TO OTHER CELLS
One of the most widely used cancer chemotherapy agents not only kills cells directly, but also appears to cause cells to transmit a "death signal" to neighboring cells, according to a Yale researcher. The agent, cisplatin, has been used in cancer chemotherapy for over 30 years and is effective in the treatment of testicular, lung, head, neck, cervical, and ovarian cancers, among others. It played a major role in the recent recovery from testicular cancer of champion cyclist Lance Armstrong. However, the response to cisplatin varies from patient to patient and many tumors develop resistance over time. The study was intended to understand how cisplatin kills cancer cells. The senior author of the study, Peter Glazer, M.D., professor and chair of the Department of Therapeutic Radiology at Yale School of Medicine, Chief of Therapeutic Radiology at Yale-New Haven Hospital and an attending radiologist on the medical staff said the "death signal" is only active when the cells are at high density, touching each other. The cells then communicate between gap junctions, which are small tunnels where cell molecules pass between cells. "By careful attention to cell growth conditions, we found that treatment of monolayer cells at high density with cisplatin results in greater cell killing than when the same cells are treated at low density with the same dose of drug and then handled in the same way. This is consistent with a cell-interdependent mechanism of cell death," he said. "Right now we think this action is unique to cisplatin." The new pathway appears to require the activity of DNA-dependent protein kinase, an enzyme already known to play a role in the DNA damage response. Glazer said he and his co-author, Ryan Jensen, discovered the new pathway for cisplatin while studying tumor cells cultured at different densities and treated with various cancer therapy agents.
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