High
levels of high density lipoprotein (HDL), also known as the "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.
Recently,
a team of researchers led by Philippe Frank, Ph.D., a cancer biologist in the
Department of Biochemistry and Molecular Biology at Thomas Jefferson University, 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.
The team said, 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.
To study the effect of HDL on cancer cells at the molecular
level, Dr. 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 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.
