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Pathways to Discovery: Spring 2012

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Fat Cells Fuel Ovarian Cancer Growth

The cancer cells go where the food is.
—Ernst Lengyel, MD, PhD

Ovarian cancer is dubbed the"silent killer" because it often goes undetected until it has spread extensively; therefore, the ability to control or prevent metastasis would provide a significant advantage in treating ovarian cancer.

Researchers at UChicago are moving in that direction because they have determined why tumor cells migrate to the omentum—tissue that stores fat and protects abdominal organs—and how the tumors use fat cells to fuel their growth.

When Ernst Lengyel, MD, PhD, professor of obstetrics and gynecology, watched surgeries as a resident, he wondered why most ovarian cancer spread to the omentum.

Little was known about the process except that once the cancer metastasized to the
omentum, it grew fast. This rapid growth contributes to the high mortality rate that results from ovarian cancer.

With these clinical observations, Dr. Lengyel set out to investigate the interaction
between ovarian cancer and the omentum. What he and his research team saw was that the cancer cells seemed to be attracted to adipocytes, cells that store fat. They injected ovarian cancer cells into the abdomens of healthy mice and saw that the cancer cells reached the omentum within 20 minutes. They found that the cancer cells used fat cells for energy, acting as "jet fuel" for cancer growth, as Dr. Lengyel described.

"The cancer cells go where the food is," he said. "It's a very natural selection,
since fat is the highest and most energycontaining substrate we have in the body."
The study, which was published in Nature Medicine, illustrates how the tumor's microenvironment may play a bigger role in metastasis than previously suspected.

Potential for New Treatments
Next, the researchers repeated the experiment on genetically modified mice that
lacked a protein expressed by fat cells that is responsible for shuttling fat, called fatty acid binding protein 4 (FABP4). The researchers found that the cancer cells did not grow as well on the omentum, suggesting that FABP4 may be a target for treatment.

"If you can stop the cells from growing there, you can prevent a major site of
metastasis," said Kristin Nieman, PhD, a postdoctoral fellow and lead author of
the study. "Hopefully, this will change the paradigm for ovarian cancer, which has
not had many new treatments." Current treatment for ovarian cancer is tumor debulking surgery and chemotherapy.

Further studies will determine how these findings can benefit patients, as well
as how cancer cells adjust their metabolism when they interact with fat cells.

Dr. Lengyel said, "It should be helpful to study and understand this mechanism in other tissues that have adipocytes, such as breast and brain tissue."

Ernst Lengyel