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Spring 2000

Research Magazine > ARCHIVE > Summer 99 > Article

Marked for Cancer
by Paul Karr

More than just professional determination motivates Michael Pierce to piece together the cellular relationships that might one day lead to an early-detection blood test for cancer.

The biochemist and molecular biologist at UGA's Complex Carbohydrate Research Center, whose father died of a highly metastatic cancer in 1982, said the work began as a personal crusade.

"[My father's death] really galvanized my interest in what happens on cell surfaces during tumor formation and metastasis," he said.

Pierce has developed a specialty of studying a particular enzyme in the body that may prove useful as an early marker for detecting pancreatic and breast cancers. The enzyme, N-Acetylglucosaminyl-transferase (GNT-5 for short), is produced in larger quantities in many kinds of human cells when they begin turning cancerous. As it is produced, the structure of carbohydrates on those cancer cell surfaces begins to change, and these changes may affect the way the cells become invasive and metastatic.

To develop a test for the tongue-twisting enzyme as a potential cancer marker, Pierce and his team knew they first would need to figure out the precise structural changes that occur in cell surface carbohydrates when a cell in the body becomes cancerous. That meant they would need enough of the rare GNT-5 to use experimentally.

An American Cancer Society Faculty Research Award and a National Cancer Institute grant helped fund Pierce's early work of extracting, purifying and then carefully working out the genetic sequence. The research proved fruitful when the UGA team became the first in the world to clone it.

"The molecular cloning was enormously difficult," said Pierce, who published his breakthrough in late 1993, "because GNT-5 turns out to be one the largest enzymes of this type. We had no idea of its size or structure at the outset. And the bigger they are, the more complicated it is to clone them."

That accomplished, Pierce's team has since turned to the equally difficult job of finding ways to detect increases in GNT-5 in potential cancer cells in the body and traces of them in blood. A Chinese colleague has developed a blood test based on GNT-5 and related enzymes that can detect developing pancreatic cancers - especially virulent, since they show almost no symptoms until it is too late to treat them as small as two centimeters across. Pierce said he thinks he can refine that test up to one hundredfold. And he is encouraged by other preliminary findings that eventually might lead to a GNT-5-based test that would serve as an early breast-cancer screen.

Such tests would use lectins - proteins extracted from plants - to locate certain unique carbohydrates on the glycoproteins that cancer cells secrete into the bloodstream. Scientists already have uncovered one of these so-called "reporter proteins" for pancreatic cancer, but markers for breast cancer haven't been found yet. The next step of Pierce's research will be to identify potential markers. Then, if all goes well, he will work to determine whether those markers are present in the blood secreted by the cancerous cells.

E-mail hawkeye@arches.uga.edu or access http://bmbiris.bmb.uga.edu/pierce/website/ for more information.


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