CCIL Students Explore Link Between Ovarian Cancer and Cholesterol

By Tyler Wolpert
July 23, 2019

Ovarian TeamThe statistics behind ovarian cancer are grim: roughly 23,000 new patients are diagnosed each year, and the five-year survival rate is less than 50%.

The disease is difficult to diagnose—its vague, flu-like symptoms are often attributed to more common ailments, and diagnostic testing frequently does not catch it in its early stages. Treatments, involving surgery and chemotherapy, are not especially effective and often have debilitating side effects and dismal outcomes. 

“This type of cancer has a high mortality and recurrence rate,” said Sisi He, a member of the C STAR graduate student program. “New therapeutic and lifestyle strategies are a must if we want to prolong progression-free survival. So many people suffer from this disease, and I want to perform research that will result in less suffering.”

He’s work focuses on cholesterol’s effect on ovarian cancer progression and survival. Her advisor, Erik Nelson, an assistant professor of molecular and integrative physiology, previously discovered that cholesterol, and it’s metabolite 27-hydroxycholesterol (27HC), affects breast cancer progression. 

“When I came into his lab,” said He, “we were curious if cholesterol affected ovarian cancer as well, and if so, what is the molecular mechanism behind it.”

Cholesterol breaks down in the body through an enzyme called CYP27A1, which is associated in patients who have a poor survival rate. This enzyme converts cholesterol into 27HC, and researchers conjecture that this product drives ovarian cancer cell growth through the tumor microenvironment—the blood vessels, immune cells, and other elements that surround and interact with a tumor.

To test this, He’s team implanted ovarian cancer cells into two groups of mice: normal ones and those that lacked CYP27A1. They then fed the mice a high-cholesterol diet and monitored the results. Helping with this part of the study was Joy Chen, an undergraduate student in the CCIL’s Cancer Scholars program, who performed the tumor implantation procedures.

“Before joining this lab, I’ve never worked with mice before,” said Chen. “Assisting with the surgeries and data analysis was interesting, and I was able to learn a lot through the process.”

Incorporating undergraduate students like Chen into research has many benefits for both graduate researchers and faculty members.

“Students bring tremendous enthusiasm and the spark for research into the lab,” said Nelson. “They often bring a fresh perspective and may bring up things you would not have thought about otherwise.”

After implanting the tumors, He and the team observed that they grew aggressively in the normal mice but developed only slightly and then regressed below detection levels in the mice that lacked CYP27A1. This indicated that the enzyme and its interaction with cholesterol may be necessary for tumor growth, and its presence could lead to a worse prognosis.

Further exploration is necessary—even though the researchers found that 27HC can affect the immune system, the exact process is unclear. He’s team wants to determine how it suppresses the immune system and validate the findings in samples from human patients.

If the findings are validated, the work may ultimately lead toward more targeted ovarian cancer treatments in the future. “Since our findings suggest that cholesterol plays a role in ovarian cancer progression and survival, we might be able to target the disease through lifestyle changes and cholesterol-lowering drugs,” said He.

Through a partnership with Carle Foundation Hospital, He is now working to confirm her findings in human samples. “We’re analyzing patient data and tumor samples to see if we can confirm our observations that cholesterol is associated with a suppressed tumoral immune system environment. I’m very excited to see what we’ll find,” said He.

The National Institute of Health and the Cancer Scholars for Translational and Applied Research supported this research. Find the paper “Host CYP27A1 expression is essential for ovarian cancer progression” at go.illinois.edu/CYP27A1.