Research Horizons, July 09 - Unlike many cancer biology researchers who investigate general processes underlying many cancers, John McDonald focuses his investigations broadly on one type of cancer - ovarian.

Ovarian cancer is the most lethal gynecological cancer, with the American Cancer Society predicting that in the United States alone each year, more than 20,000 women will be diagnosed with ovarian cancer and 16,000 will die from it.

"Ovarian cancer is called the silent killer because by the time symptoms arise and it's detected, it has typically spread throughout the body," says McDonald, chief scientist of the Ovarian Cancer Institute and associate dean for biology development in the School of Biology. "Our laboratory takes an integrated approach to studying ovarian cancer by investigating its causes, establishing accurate and reliable diagnostic tests, and developing novel and effective therapies."

One focus of McDonald's research is to determine how cancer cells develop in the ovaries. While it is estimated that up to 90 percent of ovarian carcinomas are derived from ovarian surface epithelial cells â€" cells that create the thin layer of tissue that covers the ovaries â€" the behavior of these cells differs from other epithelial-derived carcinomas because they become more specialized as malignancy progresses.

To investigate this behavior in more detail, McDonald and Nathan Bowen, a research scientist and Georgia Cancer Coalition Distinguished Cancer Scholar, compared the gene expression profiles of ovarian surface epithelial cells isolated from the surface of healthy ovaries with those of malignant ovarian tumors collected by the Ovarian Cancer Institute.

The results showed that more than 2,000 genes were expressed at significantly different levels in the two sample types. Genes associated with adult stem cell maintenance were expressed at a much higher level in the cells isolated from healthy ovaries.

"We found that changes in the expression of genes involved in maintaining the inertness and stem cell nature of epithelial surface ovarian cells may be instrumental in the initiation and development of ovarian cancer," explains McDonald.

The results also showed that the surface of the ovary exhibits the characteristics of an adult stem cell niche, which is a protected environment where stem cells remain inactive until a signal triggers their cell cycle and they differentiate.
Expanding on these results, McDonald, Bowen and postdoctoral fellows Roman Mezencev and Lijuan Wang are currently examining the sensitivity of ovarian cancer stem cells and differentiated cancer cells to existing chemotherapy agents.

"The preliminary results indicate that existing chemotherapy agents may effectively kill cancer cells but not touch these cancer stem cells, which could be why ovarian tumors and other cancers frequently recur," adds McDonald.

This work was supported by the Ovarian Cancer Institute, Georgia Cancer Coalition, Golfers Against Cancer Foundation, Ovarian Cycle Foundation, Robinson Family Foundation and Deborah Nash Harris Foundation.

By Abby Vogel
Photo By Gary Meek