FEATURE ARTICLE
Metastasis
The spread of cancer cells to distant sites implies a complex series of cellular abnormalities caused, in part, by genetic aberrations
Cornelis J. Van Noorden, Linda Meade-Tollin, Fred Bosman
Diet and Cancer
In the future, the question of how to treat cancer and its spread may take a back seat to strategies that prevent its development altogether. Scientists have increasingly discovered links between the environment, diet and the health of the individual. The hope in all of these studies is to eliminate the environmental dangers and educate individuals about how they can protect themselves and their bodies from agents that promote cancer.
Recently, much research has focused on dietary nutrients that might actually protect people from developing cancer. Among the agents under exploration are vitamins E and C, selenium, wine and substances from plants, called phytochemicals.
In the Van Noorden laboratory, we are looking at the relation between fatty acids, cancer and metastasis. We have found that omega-3 polyunsaturated fatty acids (PUFAs), which are found in fish such as salmon and mackerel, may help to prevent the development and progression of primary cancers, whereas omega-6 PUFAs from plants actually seem to promote tumor growth. It was recently demonstrated by us that omega-3 PUFAs inhibit proliferation of normal cells in vivo, whereas omega-6 PUFAs did not affect cell proliferation very much.
These effects can be explained by the formation of lipid peroxidation products that can damage DNA when it is uncovered during the cell cycle. Therefore, lipid peroxidation is kept to a minimum during the cell cycle of normal cells. However, lipid peroxidation products are generated in large amounts in cells that contain high levels of omega-6 and omega-3 PUFAs. Our investigations indicate that the inhibiting effect of omega-3 PUFAs on cell proliferation is mediated by lipid peroxidation products.
Since PUFAs seem to be important in preventing primary cancers, members of the Van Noorden laboratory were interested in seeing whether they had any effect on reducing metastatic tumors. Specifically, we explored the effect of PUFAs on colon cancers that metastasized to the liver in rats. Quite to our surprise, we found that, in rats, fish-oil treatment actually promoted the development of metastatic tumors in the liver. In fact, the results were dramatic. Fish oils caused a 10-fold increase in the number of tumors and a 30-fold increase in their size. Plant PUFAs did not affect the number of tumors, but their size was increased by 10-fold, as compared with animals on a low-fat diet. We believe the fish oils had the effect they did because the liver tumors were completely lacking the connective tissue known as stroma, which is normally found in and around tumors. It seems that tissues often try to encapsulate the tumor in stroma to limit its spread into the tissue. Our results would suggest that stroma formation is far more important in defending the tissue from cancerous invasion, at least in the liver, than we previously appreciated.
Our data also show that omega-3 PUFAs have at least two contradictory effects in relation to metastases in the liver. First, omega-3 PUFAs restrict cellular proliferation, as was shown in the first study. However, they also have the effect of inhibiting stroma formation in and around the tumors. This latter effect means that tumors can grow much faster in spite of the fact that omega-3 PUFAs inhibit cellular proliferation. We are now designing studies to investigate the effects of omega-3 PUFAs in the diets of colon-cancer patients at risk of developing liver metastases.
Until such a time that scientists become informed enough to prevent cancer, it is our hope that as processes crucial for the development of cancer and metastasis are ever more clearly delineated, this understanding will lead to more rational therapies. The new therapeutic interventions discussed hold great promise for slowing down or preventing cancer progression. The next generations of these drugs and strategies may even cure the disease someday. Since metastasis is the main cause of death in cancer patients, it will be a prime target for research to develop treatments that are now so desperately needed.
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