Alcohol activates cellular changes that make tumor cells spread

Alcohol consumption has long been linked to cancer and its spread, but the underlying mechanism has never been clear.

Now, researchers at Rush University Medical Center have identified a cellular pathway that may explain the link.

In a study published in the current issue of Alcoholism: Clinical and Experimental Research, the researchers found that alcohol stimulates what is called the epithelial?to?mesenchymal transition, in which run-of-the-mill cancer cells morph into a more aggressive form and begin to spread throughout the body.

"Our data are the first to show that alcohol turns on certain signals inside a cell that are involved in this critical transition," said Christopher Forsyth, PhD, assistant professor of medicine and biochemistry at Rush University Medical Center and lead author of the study.

The epithelial-to-mesenchymal transition is a hot area of research right now, implicated in the process whereby cancer cells become metastatic. A large body of laboratory and clinical research suggests that it plays a key role in making cancer cells aggressive.

"Cancer cells become dangerous when they metastasize," Forsyth said. "Surgery can remove a tumor, but aggressive tumor cells invade tissues throughout the body and take over. If we can thwart this transition, we can limit cancer's toll."

The researchers treated colon and breast cancer cell lines with alcohol and then looked for the biochemical hallmarks of the epithelial-to-mesenchymal transition, including evidence of a transcription factor called Snail and of the receptor for epidermal growth factor. Snail controls the epithelial-to-mesenchymal transition; when overexpressed in mice, it induces the formation of multiple tumors. Epidermal growth factor is required by many cancer cells. "They need lots of it," Forsyth said. "They are addicted to it."

Laboratory tests showed that alcohol activated both these and other biochemicals characteristic of the epithelial-to-mesenchymal transition. Tests also demonstrated that the alcohol-treated cells had lost their tight junctions with adjacent cells, a preparation for migrating, as metastatic cells do.

In addition, Forsyth and his colleagues found that the same roster of biomarkers was activated in normal intestinal cells treated with alcohol, suggesting that alcohol not only worsens the profile of existing cancer cells but also may initiate cancer by stimulating the epithelial-to-mesenchymal transition.

Other researchers at Rush involved in the study were Yueming Tang, PhD, Maliha Shaikh, MS, Dr. Lijuan Zhang and Dr. Ali Keshavarzian. Research support was provided in part by the National Institutes of Health.

About Rush:

Rush University Medical Center includes a 674-bed (staffed) hospital; the Johnston R. Bowman Health Center; and Rush University (Rush Medical College, College of Nursing, College of Health Sciences and the Graduate College).

Rush is currently constructing a 14-floor, 806,000-square-foot hospital building at the corner of Ashland Avenue and Congress Parkway. The new hospital, scheduled to open in 2012, is the centerpiece of a $1-billion, 10-year campus redevelopment plan called the Rush Transformation, which also includes a new orthopedics building (to open in Fall 2009), a new parking garage and central power plant completed in June 2009, renovations of selected existing buildings and demolition of obsolete buildings. The new hospital is being designed and built to conserve energy and water, reduce waste and use sustainable building materials. Rush is seeking Leadership in Energy and Environmental Design (LEED) gold certification from the U.S. Green Building Council. It will be the first full-service "green" hospital in Chicago.

Rush's mission is to provide the best possible care for our patients. Educating tomorrow's health care professional, researching new and more advanced treatment options, transforming our facilities and investing in new technologies -- all are undertaken with the drive to improve patient care now, and for the future.

October 26, 2009