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 Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>