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Special populations: People with melanoma
Metastasis, the spread of cancer cells from a primary tumor to another site in the body, is a complex process. Researchers do not understand why a few cells metastasize while other cells do not. A study performed in mouse models suggests that high doses of some antioxidants may make it easier for cancer cells to metastasize. (12/01/2015)
Distinguishing what makes some melanoma cells capable of metastasizing while other cells are not.
While this study looks at melanoma specifically, generally knowing what allows a cell to metastasize is important for our understanding of all cancers. This knowledge will help scientists and physicians to better target and defeat cancer, as identifying factors that make cancer worse and should be avoided.
Research on the relationship between antioxidant supplements and the spread of cancer has produced mixed results. Some studies found that antioxidants suppress cancer progression, while others showed that it increases new cancers. Clinical trials have determined that increasing dietary antioxidants does not reduce cancer incidence. On the contrary, some doses of antioxidant supplements have been shown to increase the incidence and death from prostate and lung cancers. It is also important to remember that the doses of antioxidants used in this study and others like it were designed for treatment, and were therefore much higher than what would normally be consumed in a healthy diet. Dietary antioxidants are not only safe, they are also beneficial. You should discuss consuming dietary antioxidants and any supplements you take with your health care provider.
Cells undergo a process called metastasis to spread from a primary tumor to other sites in the body. Few cancer cells can survive the metastasis process to spread and grow at another site in the body. It is not fully understood how cells that manage to metastasize are able to do so. Dr. Sean Morrison and colleagues at the University of Texas Southwestern Medical Center looked at the capability of metastasized melanoma cells to withstand oxidative stress. (Oxidative stress, which can damage cells, occurs when an imbalance develops between reactive oxygen species (ROS) and the body’s ability to remove them.) ROS occurs naturally in the body as oxygen is processed; they are damaging, but our bodies usually have a sufficiently strong system response to handle it. ROS increase during times of environmental stress, such as exposure to ultraviolet (UV) light or ionizing radiation. Molecules called antioxidants play a role in controlling ROS. Antioxidants are produced by the body and are also found in many different foods. Some antioxidants are sold as over-the-counter dietary supplements.
How oxidative stress and antioxidants affect the ability of melanoma cells to metastasize.
Cancer cells from four patients with non-metastatic melanoma and four patients with metastasized melanoma were injected into mice that lacked functioning immune systems.
This study was done in mice that did not have functioning immune systems, allowing researchers to inject and study human tumor cells in a mouse model. Though the researchers used melanoma cells from human patients samples, observing what happens when they were transplanted into immunodeficient mice does not exactly correlate to what happens in human cancer patients with functional immune systems. In addition, the number of different patient samples used in this study was relatively low, which means that there is a possibility that the results the researchers see are unique to those tumors. Researchers did note that melanoma metastasis in the study mice is predictive of clinical outcomes—in other words, the cancer cells that metastasized in human patients also metastasized in the mice. While this may be true, it does not mean that the mechanism that the cells use to metastasize is exactly the same in the two species, or that a functional immune system may affect the process.
Not too long ago, the idea that antioxidants are beneficial was well received, and clinical trials looked at giving cancer patients supplementary antioxidants. Recently, however, this idea is being questioned. This study indicates that oxidative stress limits the ability of melanoma cells to metastasize; when researchers added antioxidants to relieve oxidative stress, more metastasis occurred. The antioxidant treatments used in these mouse studies may help us understand how cancer acts, but the path from antioxidant treatments in genetically altered mice to clinical application is a long one, and not all study results in mice hold true in human patients. More work needs to be done to fully understand this process and how it might impact cancer patients.
However, the data from previous clinical trials prompted the U.S. Preventive Services Task Force (USPSTF) to recommend against the use of Vitamin E and Beta-carotene (antioxidants) for the prevention of cardiovascular disease or cancer. The USPSTF also says that there is not enough data to recommend for or against the use of multivitamins (which include antioxidants) for the prevention of cardiovascular disease or cancer.
It is also important to note that the antioxidants injected into mice in this study were pure, supplemental treatment antioxidants. They included much greater antioxidant levels than what a person would get from a normal, healthy diet. In the context of this study, a greater dose of treatment antioxidants promoted metastasis. People with cancer, and those who have a high risk of cancer, should continue to eat a healthy diet that includes a variety of fruits and vegetables.
Piskounova E, Agathocleous M, Murphy MM, et al. “Oxidative stress inhibits distant metastasis by human melanoma cells.” Nature (2015) 527: 186-91.