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. Now, 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.
"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 Dr. Frank. The work was published online September 24th in the journal Breast Cancer Research.
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.
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," says Dr. Frank. “We hope this study will lead to the development of new drugs targeting SR-BI or cholesterol metabolism and eventually preventing tumor progression,” he adds.
The authors declare that they have no conflicts of interest.
Dr. Frank receives funding from The Susan G. Komen Foundation and the NIH.For more information, contact Edyta Zielinska, (215) 955-5291, firstname.lastname@example.org.
Edyta Zielinska | EurekAlert!
Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München
Second cause of hidden hearing loss identified
20.02.2017 | Michigan Medicine - University of Michigan
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
22.02.2017 | Power and Electrical Engineering
22.02.2017 | Life Sciences
22.02.2017 | Physics and Astronomy