Two new mouse studies have provided insight into the role of the death-inducing protein TRAIL and its receptors in tumor development and metastasis.
Binding of TRAIL to its receptors induces the cells expressing the receptors to undergo a form of cell death known as apoptosis. Wafik El-Deiry and colleagues from the University of Pennsylvania, Philadelphia, found that if lymphoma-prone mice were deficient in the TRAIL receptor they developed lymphoma more frequently than TRAIL receptor--sufficient lymphoma-prone mice. In addition, the lymphoma was more likely to metastasize.
Consistent with these effects in lymphoma-prone mice, normal mice deficient in the TRAIL receptor developed more irradiation-induced lung tumors and more chemical-induced liver tumors than normal TRAIL-sufficient mice.
Further analysis showed a role for the TRAIL receptor in controlling chronic inflammation, leading the authors to suggest that the TRAIL receptor functions as a suppressor of inflammation and tumor development in multiple tissues.
Using a multistage model of squamous cell skin cancer, a team of researchers from the German Cancer Research Center, Heidelberg, and the Fred Hutchinson Cancer Research Center, Seattle, found a role for the TRAIL receptor in tumor metastasis but not primary tumor development.
TRAIL receptor--deficient mice treated with a chemical on the skin, developed tumors at the same rate, and tumors of the same size, as normal mice. However, the skin tumors in the TRAIL receptor--deficient mice metastasized to the lymph nodes more frequently, leading the authors to suggest that agonists of the human receptors for TRAIL might reduce the incidence of metastasis.
Journal article: TRAIL-R deficiency in mice promotes susceptibility to chronic inflammation and tumorigenesis. Journal of Clinical Investigation. January, 2008.
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