Research recently published online in Epidemiology, Biomarkers & Prevention, provides evidence that colon cancer may be caused in part by a decrease in production of the hormone guanylin.
Some cancers are driven by hormones, for example breast cancer is driven by estrogen and prostate cancer by testosterone; yet to date, none were believed to be driven by a lack of hormone. Evidence now suggests that human colon cells may become cancerous due to an inability to produce guanylin, a hormone that assists cells in maintaining their normal biology.
Guanylin is a locally acting hormone produced by the colon cells that it acts upon. The hormone is known to activate a receptor termed GUCY2C, the signaling of which is crucial in both the replenishment of the skin cells lining the gut and maintenance of their overall function. The skin of the gut turns over approximately once every 3 days, therefore adequate control and maintenance of the signals that replenish the skin is of utmost importance. In the absence of signals that maintain division, aberrant cell division becomes more likely, which can lead to cancer.
These diminished levels of guanylin lead to an increased production of GUCY2C receptors by the colon cells, in an attempt to catch any possible signal from outside the cell. Therefore, many colon cancers exhibit high numbers of GUCY2C receptors.
Researchers at Thomas Jefferson University (PA, US) examined colon cancer samples from 281 patients, comparing tumor tissue with nearby noncancerous colon tissue. They found that guanylin production – measured by the number of mRNAs for guanylin contained in each cell – decreased 100–1000 times in over 85% of the colon cancers tested. “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,” stated Scott Waldman (Thomas Jefferson University), senior author of the research.
The team also demonstrated that in individuals over 50 years of age, guanylin production was reduced in normal colon cells, which could provide a reason for the increased risk of developing colon cancer in this population.
If the initial findings are validated by further studies, replacement of the hormone could potentially be utilized as a treatment for patients at high risk of developing colon cancer. “We could prevent colon cancer by giving patients hormone replacement therapy with guanylin,” added Waldman.
Waldman believes that the next step is to test whether hormone replacement can prevent colon cancer development/growth in mice. The team is also working on understanding precisely how guanylin functions in order to maintain the normal health of colon cells.
Sources: Hormone loss could be involved in colon cancer; Wilson C, Lin E Jieru, Li Peng et al., The paracrine hormone for the GUCY2C tumor suppressor, guanylin, is universally lost in colorectal cancer. Cancer Epidemiol. Biomarkers doi: 10.1158/1055-9965.EPI-14-0440 (2014) (Epub ahead of print).