True Believer

A link between cancer and stem cells: religion or science?

One of the most contentious theories in cancer research today is that tumor development, growth and metastasis can be blamed on cancerous, nonembryonic stem cells. The fact that cancer recurs when standard treatment stops is further evidence that stem cells are behind the process, the theory's proponents insist.

If this hypothesis is more religion than science, as skeptics argue, then count physician-scientist Courtney Houchen, M.D., associate professor of medicine-gastroenterology, as a true believer.

Houchen's epiphany came when he was able to grow new epithelial cells on the backs of nude mice. Here was proof he had found a stem cell marker that allowed him to distinguish stem cells from their ordinary offspring, isolate them and use them to cause growth on those mice.

The link to cancer came when Houchen's lab found the same stem cell marker - DCAMKL-1 - expressed in a variety of malignant tumors. Use of a reagent to block the expression of RNA for this protein led to the discovery that blocking DCAMKL-1 appears to reduce tumor growth in the colon and pancreas.

"These data strongly suggested that this protein is not only a marker of these stem cells, but likely plays a key functional role in normal intestinal growth and tumor progression," Houchen said.

As a cancer stem cell marker, DCAMKL-1 could eventually be a novel target for anti-stem cell-based therapies for certain cancers, he added.

"We have advanced this stem cell research through a lot of controversy," Houchen said. "When we first identified this marker, we thought it was all pretty straightforward. This was (an area in the colon) where stem cells are supposed to be, but we had trouble getting it accepted by the scientific community.

"We had to do many, many experiments to find out the function of this protein so we could prove it was involved in cancer and on normal stem cells."

Houchen said it appears that the ability of stem cells to promote several types of cell growth could explain how cancer metastasizes.

Another characteristic of stem cells - that they divide slowly - explains how they can avoid chemotherapy and radiation, which target rapidly dividing cells, and survive to cause cancer to recur.

Houchen's contribution to a recent increased interest in stem cells' link to cancer also came in the discovery by him and longtime former colleague, Shrikant Anant, PhD, now at the University of Kansas, of a second stem cell protein. This protein turns off a natural tumor suppressor and turns on a cancer-causing gene. It was the first evidence of a stem cell protein's regulation of a tumor suppressor.

Houchen, who holds the Frances and Malcolm Robinson Chair in Gastroenterology, has recently received grants of $192,215 from the Oklahoma Center for Adult Stem Cell Research and $300,000 over three years from the Oklahoma Center for the Advancement of Science and Technology to continue his stem cell research. The OCAST grant was matched by the VA Medical Center and ADNA Inc. He and Russell Postier, MD, chair of the Department of Surgery, have also received a National Institutes of Health Exploratory/Developmental Research grant of $382,000 from the National Cancer Institute to study pancreatic cancer stem cells.