UGA researchers discover potential target for colon cancer treatment

Researchers at the University of Georgia have discovered that a specific sugar molecule plays a major role in the development of colon cancer, opening the doors for the possibility of new therapeutic treatments that may help reduce chances of disease recurrence.

In a paper published recently in the Journal of Biological Chemistry, the research team demonstrates that the sugar molecule, made by an enzyme known as GnT-V, regulates the development of a particular subset of cancerous cells known as cancer stem cells.

Much like normal stem cells that sustain organs and tissues, cancer stem cells can self-renew, and their cellular offspring clump together to form tumors. Conventional treatments like surgery, chemotherapy or radiation may reduce overall tumor size, but if they do not kill the cancer stem cells, the disease is likely to return.

“You can think of it like a colony of ants,” said Michael Pierce, director of UGA’s Cancer Center, Mudter Professor in Cancer Research in UGA’s Complex Carbohydrate Research Center and principal investigator for the study. “You can kill the ants in the mound, but if you don’t get the queen, they will come back.”

In 2011, an estimated 1,162,426 people were living with colon and rectal cancer in the United States, according to the National Cancer Institute. While death rates have fallen over the past several years, colorectal cancers still claim about 50,000 lives each year.

In their experiments, researchers used mice that closely mirror colon cancer disease progression in humans. One set of mice received injections of non-modified human cancer cells, while a second received cancer cells with increased levels of GnT-V.

Mice who received cancer cells that overexpressed GnT-V were significantly more likely to develop cancer, and tumor growth was considerably accelerated.

However, mice that received injections of cancerous cells that had been specially treated to reduce levels of GnT-V not only had greater survival rates, but also developed much less aggressive cancerous tumors. 

“GnT-V regulates a kind of cellular communication pathway known as Wnt, which controls signals passing from the cell’s surface to its interior,” said Huabei Guo, assistant research scientist and lead author of the paper. “Our experiments suggest that changes in this pathway are responsible for the changes in size and number of colorectal tumors in our tests.”

Their discovery paves the way for new cancer treatment methods specifically designed to inhibit GnT-V, which, when combined with other treatments, may help prevent disease recurrence.

While their study focused particularly on colorectal cancers, the researchers hope their discovery may one day work for a variety of cancer types.

“This is a rapidly growing field within the cancer research community,” said Pierce, who is also a Distinguished Professor of Biochemistry and Molecular Biology in UGA’s Franklin College of Arts and Sciences. “We want to know what makes these cancer stem cells unique and what we need to do in order to target them specifically so we can develop new treatments and save lives.”

For a full version of the paper, see http://www.jbc.org/content/early/2014/10/01/jbc.M114.602680.short#ref-list-1

Research reported in this article was supported in part by grants from the National Institutes of Health under grant numbers U01CA128454 and P41GM103490.

The Complex Carbohydrate Research Center (pictured above) was founded at the University of Georgia in 1985, and is one of only three centers worldwide dedicated to the study of complex carbohydrates, which play critical roles in cellular communication, gene expression, immunology, organism defense mechanisms, growth and development. The 140,000 square-foot facility is home to 17 interdisciplinary research groups, including four federally designated centers for carbohydrate research. In addition to UGA research projects, the center also provides analytical services and training to university, government and industrial scientists interested in complex carbohydrate molecules. For more information about the center, see ccrc.uga.edu.