UGA researchers 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 demonstrated 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, according to Michael Pierce, director of UGA’s Cancer Center.
“You can think of it like a colony of ants,” said Pierce, who also is the 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 1.16 million people were living with colon and rectal cancer in the U.S., 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 nonmodified 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, an 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.