New evidence suggests that human colon cells may become cancerous when they lose the ability to produce a hormone that helps the cells maintain normal biology. If verified by further studies, it suggests that treating patients at high risk for colon cancer by replacing the hormone guanylin could prevent the development of cancer.
Some cancers such as breast and prostate cancer are driven by hormones, such as estrogen and testosterone, but to date, no cancers are known to be driven by the lack of a hormone.
The researchers at Thomas Jefferson University in Philadelphia, Pennsylvania, examined colon cancer samples from 281 patients and compared those tissues to nearby colon tissue that was not cancerous. They found that guanylin production, which was measured by number of messenger RNAs for guanylin contained in each cell, decreased 100 to 1,000 times in more than 85% of colon cancers tested. They verified their results by also staining for the guanylin hormone production in slices of the tissue samples. They could detect no guanylin hormone in the cancer samples.
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In addition, the researchers found that people older than 50 years produced much less of the hormone in their normal colon cells, which could help explain the increase in colon cancer risk in older people. The research was published in Cancer, Epidemiology, Biomarkers & Prevention (2014; doi:10.1158/1055-9965.EPI-14-0440).
“The fact that the vast majority of cancers stop producing this hormone leads us to believe that guanylin may be driving the growth of the tumors,” said senior author Scott Waldman, MD, PhD, of Thomas Jefferson University. He added that, if confirmed, “We could prevent colon cancer by giving patients hormone replacement therapy with guanylin.”
Colon cancer is the second leading cause of death from cancer for men and women and expected to cause 50,000 deaths in 2014, according to the American Cancer Society.
Earlier work has shown that guanylin is a locally acting hormone, produced by the very cells it acts on. Guanylin activates a receptor called GUCY2C (pronounced goosy toosy by researchers). GUC2YC signaling is critical to helping replenish the skin cells lining the gut, and maintaining their overall function. Since the skin of the gut turns over about once every 3 days, the proper control and maintenance of the signals that replenish the skin is essential. Without signals that maintain cell division, aberrant cell division is more likely to occur, which can lead to cancer.
When guanylin is diminished, the cells of the colon produce more GUCY2C receptors in order to try to catch any possible signal from outside of the cell. As a result, many colon cancers exhibit high numbers of GUCY2C receptors, despite the fact that the receptors no longer receive the hormone signal that help them activate programming that maintains the health and normal function of the cell.
The next steps, said Waldman, are to test whether hormone replacement can prevent colon cancer development and/or growth in mice, which could then be followed by tests in humans. In addition the team is working on understanding how exactly guanylin functions to maintain the normal health of colon cells.
