Brain metastasis is a terrifying complication of advanced breast cancer, with a grim prognosis and few treatment options. The cancer's spread to the brain is often undetected until patients start to develop symptoms such as seizures, headaches, and trouble thinking. Scientists hope a better understanding of the molecular events that regulate brain metastasis will lead to earlier diagnosis and improved therapies.
Using cell models, the researchers found that breast cancer cells harness a protein called alphaB-crystallin to help them stick to endothelial cells that line the small blood vessels in the brain. In addition, this protein enhances the penetration of breast cancer cells through the blood-brain barrier, which normally prevents cells and many molecules from entering the brain. Once in the brain, the breast cancer cells are able to form metastases.
The study, published in Clinical Cancer Research, and featured on the journal cover, was led by Dr. Vincent Cryns, professor of medicine at the University of Wisconsin School of Medicine and Public Health and a member of the University of Wisconsin Carbone Cancer Center.
Cryns and his colleagues also developed new mouse models of breast-cancer brain metastasis that mimic many features of the human disease. They found that reducing the expression of alphaB-crystallin in breast cancer cells hindered the cells' ability to form brain metastases in mice.
"These observations in our mouse models suggest that alphaB-crystallin may be a promising drug target that should be explored further," said Cryns. "Although there are no drug inhibitors of this protein currently, we are actively pursuing studies to identify drugs that might reduce the expression of the protein or block its effects," he added.
In addition, by examining tissue from breast-cancer patients who developed brain metastasis, the investigators discovered that women with breast tumors that expressed alphaB-crystallin had a shorter survival than women with breast tumors that did not express this protein. These studies were conducted in collaboration with researchers at the University of North Carolina at Chapel Hill, Duke University and other institutions.
Furthermore, the team found breast tumors that expressed alphaB-crystallin were more likely to be triple-negative breast cancers—an aggressive type of cancer, which lacks three receptors (estrogen receptor, progesterone receptor and HER-2) expressed in other types of breast cancer. Triple-negative breast cancers are known to have a high incidence of brain metastasis.
"Our findings suggest that alphaB-crystallin may contribute to the tendency of triple-negative breast cancers to metastasize to the brain and to their poor prognosis," said Cryns. Yet, he cautioned these findings need to be validated in additional studies.
The research was supported by grants from the Breast Cancer Research Foundation, the National Institutes of Health, Susan G. Komen, and the Cancer and Leukemia Group B.
Lisa Brunette | EurekAlert!
3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg
Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology