Does Good Cholesterol Increase Your Breast Cancer Risk?

Jefferson researchers identify a receptor for HDL that appears to make breast cancer more aggressive and that could lead to new treatments

Phillipe Frank, PhD

Philippe Frank, PhD

You’ve heard that high levels of so-called good cholesterol – high density lipoprotein (HDL) – protects against heart disease.

But perhaps what’s good for one disease may not be good for another.

High levels of HDL have been linked to increased breast cancer risk and to more aggressive breast cancer in animals.

Now, a team of researchers led by Philippe Frank, PhD, a cancer biologist in the Department of Biochemistry and Molecular Biology at Jefferson, has shown that an HDL receptor found on breast cancer cells may be responsible for this effect.

And that in turn has raised the possibility of a new molecular target that could help treat breast cancer.
“If we can block the activity of the HDL receptor in breast cancer, we may be able to limit the harmful effects of HDL, while maintaining levels that are beneficial for blood vessels,” he says.

This research was recently published online in the journal Breast Cancer Research.

To study the effect of HDL on cancer cells at the molecular level, Frank and his colleagues exposed breast cancer cell lines to HDL and found that signaling pathways involved in cancer progression were activated. The cancer cells began to migrate in an experimental model mimicking metastasis.

The researchers then limited the expression of the HDL receptor called SR-BI in the cells using silencing RNA to reduce the receptor’s levels. In response, the activities of the signaling pathways that promote tumor progression were reduced.

In addition, cells with fewer SR-BI receptors displayed reduced proliferation rates and migratory abilities than cells with normal SR-BI levels.

Most importantly, reduced SR-BI levels were associated with reduced tumor formation in a mouse model of tumorigenesis. The researchers then blocked the SR-BI receptor in a breast cancer cell line with a drug called BLT-1 and noticed reduced proliferation and signaling via proteins linked to tumor formation.

This study supports the idea that HDL plays a role in the development of aggressive breast cancers and that inhibiting its function via SR-BI in breast cancer cells may stall cancer growth.

Additional studies will be needed to develop more specific drugs to inhibit SR-BI.

“Also, we need to understand what levels of cholesterol are required by the tumor before trying to reduce or modify lipid levels in cancer patients,” Frank says. “We hope this study will lead to the development of new drugs targeting SR-BI or cholesterol metabolism and eventually preventing tumor progression.”

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