Scientists have found that high levels of ‘good cholesterol’,known to protect against heart disease,may raise breast cancer risk and enhance cancer aggressiveness.
Researchers showed that a high density lipoprotein (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,” said lead researcher Philippe Frank,a cancer biologist in the Department of Biochemistry and Molecular Biology at Thomas Jefferson University.
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 signalling 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 using silencing RNA to reduce the receptor’s levels.
In response,the activities of the signalling pathways that promote tumour 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 tumour 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 signalling via proteins linked to tumour 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 tumour before trying to reduce or modify lipid levels in cancer patients,” said Frank.
“We hope this study will lead to the development of new drugs targeting SR-BI or cholesterol metabolism and eventually preventing tumour progression,” he added.
The study was published in the journal Breast Cancer Research.