Intestinal Barrier Walls Out Cancer

Cancer formation in distant sites associated with leaky gut

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(RxWiki News) Why cancer forms in organs at some distance from the original tumor is not fully understood. New research suggests the intestinal barrier can protect against this spread.

The hormone receptor guanylyl cyclase C (GC-C) found in the intestine is now believed to be essential in strengthening the body's intestinal barrier.

Furthermore, this wall of sorts separates the gut from the rest of the body and may keep cancer from traveling far and wide.

"See a doctor if you have inflammatory bowel disease."

Researchers from Thomas Jefferson University, led by Scott Waldman, M.D., Ph.D., chair of the Department of Pharmacology and Experimental Therapeutics, learned in a pre-clinical animal study that when GC-C is silenced, the intestinal barrier is weakened.

When the intestinal barrier becomes weak, inflammation and cancer-causing agents start to leak into the body. This in turn can damage DNA and encourage cancer to form outside the intestine in such places as the lymph nodes, liver and lung.

Just the opposite also holds true. When GC-C, which is a tumor suppressor that's present in the intestine, was stimulated in mice, the barrier became stronger and discouraged the formation of cancer outside the gut world.

Scientists have known that a weak intestinal barrier is associated with a host of diseases, ranging from inflammatory bowel disease to asthma and food allergies.

This study shows that GC-C plays a critical role in the protective strength of the intestine.

"If the intestinal barrier breaks down, it becomes a portal for stuff in the outside world to leak into the inside world," said Dr. Waldman, who is director of the Gastrointestinal Cancer Program at Jefferson's Kimmel Cancer Center. "When these worlds collide, it can cause many diseases, like inflammation and cancer," he said.

Dr. Waldman's team has previously shown how GC-C sometimes serves as a marker from metastasis in the lymph nodes. It's also been used to predict cancer risk and may be associated with obesity.

A new medication containing GC-C is close to being approved by the U.S. Food & Drug Administration (FDA) for treating constipation.

This research opens the door for future study of GC-C in disease prevention.

"We've shown that when you pull away GC-C in animals, you disrupt the intestinal barrier, putting them at risk for getting inflammatory bowel disease and cancer. And when you treat them with hormones that activate GC-C it helps strengthen the integrity of the intestinal barrier," Dr. Waldman said. "Now, if you want to prevent inflammation or cancer in humans, then we need to start thinking about feeding people hormones that activate GC-C to tighten up the barrier."

Grants from the National Institutes of Health, the Pennsylvania Department of Health and Targeted Diagnostic and Therapeutics Inc. funded this research.

Dr. Waldman is the Chair (uncompensated) of the Scientific Advisory Board of Targeted Diagnostics and Therapeutics, Inc., which has a license to commercialize inventions related to this work.

There are no patents, products in development or marketed products to declare

Last Updated:
February 21, 2012