Tumors often have phony protein receptor.
Sadly, in cancer cells, this cascade of events doesn't always start on cue. A new study suggests that tumor cells can outwit the immune system by making large quantities of a phony, ineffective version of Fas.
The immune system, which is geared to fight foreign invaders, doesn't routinely wipe out tumors because it considers them to be part of the body. Some immune system cells, however, do recognize cancer cells as abnormal and therefore as candidates for apoptosis. Even then, when these immune cells arrive to instigate the suicide program, their Fas ligand doesn't work on some cancer cells.
According to the recent study, the phony version of Fas receptors on the cancer cells binds with Fas ligand, preventing it from hooking up with real Fas receptors and from starting the apoptosis cascade, researchers report in the Dec. 17 NATURE.
Cancerous cells whose genes direct production of plenty of the decoy receptor may survive and replicate, while other cancer cells are removed by the immune system via apoptosis, says study coauthor Avi Ashkenazi of Genentech in South San Francisco, Calif.
"If that's true, and that's a big `if,' then it suggests that a tumor has the ability to keep ahead of the immune system," says Alan N. Houghton, an immunologist at Memorial Sloan-Kettering Cancer Center in New York City.
Using tissue from 23 cancer patients, Ashkenazi and his colleagues found that many tumors produced the decoy Fas but surrounding healthy tissue did not. They detected the decoy in 6 of 15 lung tumors, in 2 of 5 breast tumors, in both colon tumors examined, and in the single stomach tumor studied.
In another experiment, extra copies of the gene that encodes this decoy protein showed up in 17 of 35 lung and colon tumor samples. Noncancerous tissue samples contained no extra copies, Ashkenazi and his colleagues report.
"I found this a very exciting paper," says Douglas R. Green, a cell biologist at the La Jolla Institute for Allergy and Immunology in San Diego. The study hints that Fas and Fas ligand may play a role that is fundamental to tumor growth, he says. Perhaps for a cell to become cancerous, it needs to both activate a proliferative mechanism "and come up with a way to avoid Fas, Fas ligand, and apoptosis," he says.
Synthetic antibodies that neutralize the decoy receptor might, if given as a drug, help the immune system attack many tumors, Ashkenazi says.
The decoy itself may also prove useful in medicine. Autoimmune reactions, in which the immune system attacks cells of the body, might be shut off by doses of the decoy version of Fas, says Noel R. Rose of Johns Hopkins Medical Institutions in Baltimore.
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|Article Type:||Brief Article|
|Date:||Dec 19, 1998|
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