Cancer biologists at Thomas Jefferson University say a protein receptor for high density lipoprotein (HDL), known as good cholesterol, may make breast cancer more aggressive.
While high levels of HDL are thought to protect against heart disease, high levels of HDL have also been linked to increased breast cancer risks and to enhanced cancer aggressiveness. Now, lead researcher Philippe Frank has shown 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.
"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," says Frank.
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 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 the HDL receptor called SR-BI in the cells. 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. Most importantly, reduced SR-BI levels were associated with reduced 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. According to Frank, additional studies will be needed to develop 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," he noted. "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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Source: Thomas Jefferson University