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Does ‘Good’ Cholesterol Increase Breast Cancer Risk?

Protein receptor for HDL may make breast cancer more aggressive (October 9)

High levels of high-density lipoprotein (HDL), also known as “good” cholesterol, are thought to protect against heart disease. However, what’s good for one disease may not be good for another. High levels of HDL have also been linked to increased breast cancer risks and to enhanced cancer aggressiveness in animal experiments.

Now, researchers at Thomas Jefferson University report that an HDL receptor found on breast cancer cells may be responsible for this effect, proposing a new molecular target that could help treat the disease.

The study was published online in Breast Cancer Research.

“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," said lead investigator Philippe Frank, PhD.

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

The researchers then limited the expression of an 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 did cells with normal SR-BI levels. Most important, 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.

According to the authors, 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 inhibit cancer growth.

Source: EurekAlert; October 9, 2013.

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