Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Putting a brake on tumor spread

24.01.2014
A team of scientists, led by principal investigator David D. Schlaepfer, PhD, a professor in the Department of Reproductive Medicine at the University of California, San Diego School of Medicine, has found that a protein involved in promoting tumor growth and survival is also activated in surrounding blood vessels, enabling cancer cells to spread into the bloodstream.

The findings are published in this week's online issue of the Journal of Cell Biology.


Normal breast tissue and invasive ductal carcinoma stained brown with antibodies to activated FAK. Blood vessels are indicated by BV.

Credit: David Schlaepfer, UC San Diego.

Blood vessels are tightly lined with endothelial cells, which form a permeability barrier to circulating cells and molecules. "Our studies show that pharmacological or genetic inhibition of the endothelial protein focal adhesion kinase, or FAK, prevents tumor spread by enhancing the vessel barrier function."

The researchers found that selective FAK inhibition within endothelial cells prevented spontaneous tumor metastasis without alterations in tumor size. Schlaepfer, with colleagues at the UC San Diego Moores Cancer Center, is exploring whether inhibiting targets like FAK, which has important regulatory functions in both tumor cells and blood vessels, might provide a dual mechanism for preventing both cancer growth and spread.

Using mouse models of breast, ovarian and melanoma tumors, first author Christine Jean, PhD, showed that FAK activity was elevated in the blood vessels surrounding tumors, compared to normal tissue. FAK modifies the function of other cellular proteins, and researchers identified a previously unknown FAK target: a protein called vascular endothelial cadherin (VE-cadherin) that helps endothelial cells fasten tightly together. When modified by FAK, VE-cadherin complexes fall apart and blood vessels become leaky. Inactivating FAK within endothelial cells prevented this unwanted permeability and helped block the ability of tumor cells to pass through endothelial cell barriers.

Schlaepfer said the research has major clinical implications: Metastasis – or the spread of a cancer from its originating site to other parts of the body – is responsible for 90 percent of cancer-related deaths. "This fact alone underscores the need for a better mechanistic understanding of the metastatic process," Schlaepfer said. He noted that several FAK-inhibitors are currently being tested in clinical trials.

Co-authors include Xiao Lei Chen, Isabelle Tancioni, Sean Uryu, Christine Lawson, Kristy K. Ward and Nichol L.G. Miller, UC San Diego Moores Cancer Center; Ju-Ock Nam, Kyungpook National University, Korea; Colin T. Walsh, Binomics, San Diego; Majid Ghassemian, UCSD Department of Chemistry and Biochemistry; Patrick Turowski, University College London; Elisabetta Dejana, University of Milan; Sara Weis and David A. Cheresh, Department of Pathology, UC San Diego Moores Cancer Center.

Funding for this research came, in part, from the National Institutes of Health (grants RO1 HL093156, RO1 CA102310, and R37 CA50286), Italian Association for Cancer Research and The European Research Council, American Heart Association, Susan G. Komen for the Cure, Canadian Institutes of Health Research, Ruth Kirschstein National Research Service Award and Nine Girls Ask?

Scott LaFee | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nonstop Tranport of Cargo in Nanomachines

Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.

Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...

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.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | 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

 
Latest News

Nonstop Tranport of Cargo in Nanomachines

20.11.2018 | Life Sciences

Researchers find social cultures in chimpanzees

20.11.2018 | Life Sciences

When AI and optoelectronics meet: Researchers take control of light properties

20.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>