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Searching for Diagnostic Biomarkers for Ovarian Cancer and Placental Abnormalities

In women’s health, some of the greatest dangers lie in our inability to recognize and diagnose issues before they escalate into a life threatening condition.

Drs. Jerry Bouma and Quinton Winger, faculty in the Department of Biomedical Sciences, are working towards a solution that could give doctors and patients a leg-up in diagnosing some serious problems in women’s reproductive health.

Bouma and Winger’s research focuses on LIN28, a protein that regulates the self-renewal of stem cells. They have joined forces to better understand how this protein could hold the key for early detection of ovarian cancer and placental abnormalities in pregnancy.

The work originated when Dr. Winger was researching trophoblasts – cells formed during the early stages of pregnancy that develop into the placenta. Disrupted trophoblast cell growth and invasion is a major factor contributing to placental pathologies including preeclampsia, a condition that affects between 4-8% of all pregnancies and contributes to 20% of maternal deaths in the United States each year.

“What is important to note about these trophoblast cells is that they are invasive and migratory,” said Winger. “They invade the uterus in order to establish a placenta that grows to the right size. You have this invasion – which is a good thing – but it has to have a brake on it so that the growth doesn’t get out of hand. The placenta knows how to do that unless there is a disruption to the system.”
 
Migration and invasion can be used to describe another type of cell growth – ovarian cancer.

“Cancer cells behave very similarly to the trophoblast cells Dr. Winger is looking at,” said Bouma. “The difference is that if cancer cells decide to migrate, it is a bad thing. They don’t have that normal brake that tells them when to stop.”

As the two researchers began comparing notes, they found that these two cell types have something else in common: LIN28.

When LIN28 is present in cancer cells, it’s a bad thing because usually this is associated with “poorly differentiated” tumors and a poor outcome. Another thing that both cancer cells and trophoblast cells have in common is that these cells secrete small vesicles called exosomes, and Winger and Bouma postulate that there may be a connection between LIN28 and exosomes secreted by these cells. Importantly Winger and Bouma believe these exosomes have the potential to be used as diagnostic markers. If their theory is correct, we are one step closer to detecting ovarian cancers through a routine urine test – well before symptoms appear – or diagnosing risk of placental abnormalities in the first trimester, instead of the third.

“To date there is no treatment or method of prevention for placenta insufficiency or preeclampsia except for premature delivery of the fetus,” said Winger. “Having these markers would result in better prenatal care of patients, and would ultimately lead to detection and possible treatments before clinical symptoms.”

“In late diagnosis of ovarian cancer, usually 75-80% of patients see the cancer return after five years, and at that point it is a death sentence,” said Bouma. “If you diagnose ovarian cancer very early, you can dramatically increase positive outcomes -  success rates could be as high as 90%.”

Bouma and Winger have been collaborating on reproductive science research since 2008, co-mentoring students, and sharing lab space and other resources at the Animal Reproduction and Biotechnology Laboratory. They focus their research on topics that impact both human and animal systems.