Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stem-cell-based therapy promising for treatment of breast cancer metastases in the brain

24.04.2015

New animal model of breast-to-brain cancer spread allows testing of therapeutic stem cell approach

Investigators from Massachusetts General Hospital (MGH) and the Harvard Stem Cell Institute have developed an imageable mouse model of brain-metastatic breast cancer and shown the potential of a stem-cell-based therapy to eliminate metastatic cells from the brain and prolong survival.


Tagged therapeutic stem cells (green) are targeting breast cancer metastases (red) in the brain of a mouse model.

Credit: Khalid Shah, MS, PhD, Massachusetts General Hospital

The study published online in the journal Brain also describes a strategy of preventing the potential negative consequences of stem cell therapy.

"Metastatic brain tumors - often from lung, breast or skin cancers - are the most commonly observed tumors within the brain and account for about 30 percent of advanced breast cancer metastases," says Khalid Shah, MS, PhD, director of the Molecular Neurotherapy and Imaging Laboratory in the MGH Departments of Radiology and Neurology, who led the study.

"Our results are the first to provide insight into ways of targeting brain metastases with stem-cell-directed molecules that specifically induce the death of tumor cells and then eliminating the therapeutic stem cells."

In their search for novel, tumor-specific therapies that could target multiple brain metastases without damaging adjacent tissues, the research team first developed a mouse model that more closely mimics what is seen in patients. They found that injecting into the carotid artery breast cancer cells that express markers allowing them to enter the brain - cells labelled with bioluminescent and fluorescent markers to enable tracking by imaging technologies - resulted in the formation of many metastatic tumors throughout the brain, mimicking what is seen in advanced breast cancer patients. Current therapeutic options for such patients are limited, particularly when there are many metastases.

To devise a potential new therapy, the investigators engineered a population of neural stem cells to express a potent version of a gene called TRAIL, which codes for a molecule that activates cell-death-inducing receptors found only on the surface of cancer cells. Previous research by Shah and his colleagues had shown that two types of stem cells are naturally attracted toward tumors in the brain.

After first verifying in their model that stem cells injected to the brain would travel to multiple metastatic sites and not to tumor-free areas, the team implanted TRAIL-expressing stem cells into the brains of metastasis-bearing mice, which reduced the growth of tumors. Injecting the TRAIL-expressing stem cells into the carotid artery, a likely strategy for clinical application, led to significantly slower tumor growth and increased survival, compared with animals receiving unaltered stem cells or control injections.

The safe use of a stem-cell-based therapy against brain metastasis would require preventing the engineered cells from persisting within the brain, where they could affect normal tissue and possibly give rise to new tumors. To facilitate removal of the therapeutic stem cells from the brain at the conclusion of therapy, the researchers created cells that, in addition to TRAIL, express a viral gene called HSV-TK, which renders them susceptible to the effects of the antiviral drug ganciclovir.

Several tests in cultured cells indicated that ganciclovir would cause the death of HSV-TK-expressing stem cells, and testing in the mouse model confirmed that administration of the drug after successful treatment of brain metastases successfully eliminated therapeutic stem cells that also expressed HSV-TK.

Shah and his team are currently developing similar animal models of brain metastasis from lung cancers and from melanoma. They also are working to improve understanding of the therapeutic efficacy of simultaneously targeting multiple tumor-specific molecules on the surface of metastatic cells within the brain and anticipate that their findings will make a major contribution towards developing novel targeted therapies for metastatic tumors in the brain.

###

In addition to Shah, who is an associate professor at Harvard Medical School and a principal faculty member at Harvard Stem Cell Institute, the authors of the Brain report are co-lead authors Wanlu Du, PhD, and Tugba Bagci-Onder, PhD, along with Jose-Luiz Figueiredo, MD, and Jordi Martinez-Quintanilla, PhD - all of the MGH Molecular Neurotherapy and Imaging Laboratory. The study was supported by National Institutes of Health grants CA138922 and NS071197 and a grant from the James McDonald Foundation.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $760 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

Media Contact

Katie Marquedant
kmarquedant@partners.org
617-726-0337

 @MassGeneralNews

http://www.mgh.harvard.edu 

Katie Marquedant | EurekAlert!

More articles from Life Sciences:

nachricht Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Purdue cancer identity technology makes it easier to find a tumor's 'address'

16.11.2018 | Health and Medicine

Good preparation is half the digestion

16.11.2018 | Life Sciences

Microscope measures muscle weakness

16.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>