Researchers have discovered that tumors release fatty acids that interfere with the cells that are trying to kill them. Consequently, strategies that reduce the amount of fatty acids surrounding the tumors may give a boost to anti-cancer therapeutics. The details of these findings appear in the Journal of Lipid Research.
Several forms of anti-cancer therapy rely on what is known as immunotherapeutic anti-cancer strategies – therapies that encourage the body's natural defenses, such as cytotoxic T lymphocytes, to aid in destroying tumors. However, immunotherapeutic methods are often not effective at removing established tumors for a number of reasons, including a loss of the ability of the cytotoxic T lymphocytes to recognize the tumor and a physical barrier separating the lymphocytes and the tumor.
Now, Dr. Alan M. Kleinfeld and Clifford Okada of the Torrey Pines Institute for Molecular Studies in San Diego, CA, have added another reason to this list. They discovered that tumors secrete fatty acids which inhibit the cytotoxic T lymphocytes' ability to kill tumor cells.
"We found two things," explains Kleinfeld. "First, the most common type of free fatty acids, which at normal levels are essential for life, at high levels prevents the cytotoxic T lymphocytes from destroying tumor cells. The second thing is that human breast cancer cells, but not normal tissue from the same breast, produce very large amounts of the type of free fatty acids that block the cytotoxic T lymphocytes. Thus the cancer may have a way of defending itself against attack by the immune system, thereby reducing the potential efficacy of novel anti cancer therapies that rely on a functioning immune system."
The free fatty acids act against cytotoxic T lymphocytes by blocking a number of the lymphocytes' signaling events. For example, they keep certain proteins from being phosphorylated and they also prevent an increase in intracellular calcium that is essential for the cytotoxic T lymphocytes to kill the tumor cells. Kleinfeld suspects that these signaling events are being blocked at the cells' membranes.
These results from the Torrey Pines Institute for Molecular Studies raise the possibilities of new therapeutic targets for cancer, such as those that may transport free fatty acids out of the tumor. Alternatively, free fatty acid levels in the blood could be used to help gauge the aggressive potential of a tumor.
Journal of Lipid Research, September 2005
The American Society for Biochemistry and Molecular Biology (http://www.asbmb.org)