PHILADELPHIA, Penn. -- Interleukin-12 (IL-12), a cytokine discovered at The Wistar Institute in the mid-1980s, is known to engage in potent anti-tumor activities. Until recently, however, the biological events governing its behavior were little understood.
New information about IL-12, unearthed by scientists working in the laboratories of Dr. Giorgio Trinchieri at Wistar and Dr. William M.F. Lee at the University of Pennsylvania, will appear in the July 24 issue of Immunity.
IL-12 provokes a series of events that ultimately interfere with angiogenesis, or the formation of blood vessels that nourish and enlarge tumors. Without angiogenesis, tumors cannot thrive.
"Our findings suggest that tumor cells may have an inherent ability to produce their own antiangiogenic elements," explains Dr. Trinchieri, "and that cytokine therapy may enhance the spontaneous production of these factors. This understanding may help scientific investigators plan new therapeutic approaches to cancer."
IL-12 triggers the production of a protein, interferon-gamma (IFN- ), which in turn leads to the manufacture of a chemokine, IP-10, which blocks tumor-induced angiogenesis. To produce IP-10, however, IFN- must be able to interact directly with the tumor cells. And, if those tumor cells are genetically altered in a way that prevents them from being receptive to IFN- , their ability to hinder blood vessel formation is destroyed.
According to Dr. Trinchieri, "the ability of tumor cells to induce angiogenesis is well known, but their ability to produce antiangiogenic factors is a new finding that helps shed light on the mechanisms of anticancer therapy."
The Wistar Institute, established in 1892, was the first independent medical research facility in the country. For more than 100 years, Wistar scientists have been making history and improving world health through their development of vaccines for diseases that include rabies, German measles, infantile gastroenteritis (rotavirus), and cytomegalovirus; discovery of molecules like interleukin-12, which are helping the immune system fight bacteria, parasites, viruses and cancer; and location of genes that contribute to the development of diseases like breast, lung and prostate cancer. Wistar is a National Cancer Institute Cancer Center.
Journal
Immunity