Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Unexpected lock and key mechanism found for the assembly of tumor blood vessels

03.05.2005


A critical lock and key mechanism that allows the final step in the completion of new blood vessel formation has been identified by a University of California, San Diego (UCSD) School of Medicine team in research that promises to lead to a new way to halt tumor growth by cutting off the tumor blood supply.



The research team led by Judith Varner, Ph.D., Associate Professor of Medicine at UCSD and a member of the Rebecca and John Moores UCSD Cancer Center, made the surprising discovery that a receptor-ligand pair previously identified as key regulators of immune cell function puts the finishing touches on newly constructed blood vessels by allowing the two cell layers of blood vessels to recognize and "lock" together.

The study, which appears in the June 2005 issue of the Journal of Clinical Investigation, is the first to show how the two cell layers of blood vessels recognize and bind to each other during angiogenesis, which is the formation of new blood vessels.


The work also could yield new ways to diagnose and combat cancer. In fact, together with Barbara Parker, M.D., UCSD Professor of Clinical Medicine at the Moores UCSD Cancer Center, the researchers currently are conducting tests with breast cancer patients to see if measuring the activity of the receptor, or "lock," called integrin, could help diagnose the cancer earlier. They are also currently planning cancer clinical trials with an FDA approved drug directed against the integrin.

Angiogenesis has been an intensely studied field of cancer research for the past 10 years. Since cancer cells literally hijack the body’s normal angiogenesis process to initiate blood vessel growth to fuel the growth of tumors, researchers believe that blocking angiogenesis may choke off a tumor’s blood supply and kill the cancerous cell.

Varner and her team found that a specific integrin protein called alpha4beta1 was produced at high levels in one part of a developing blood vessel, the interior area called the endothelia. The integrin was not produced in mature blood vessels, indicating a specific role in developing vessels. The team found that the integrin was produced in the endothelia of mouse and human blood vessels that feed tumors such as colon cancer, melanoma and lung cancer. Inhibitors of the integrin stopped new blood vessel growth and suppressed tumor growth, indicating that the integrin helped in the creation of tumors

"Our study marks the first time this integrin was found to play a key role in angiogenesis," said Varner. "This integrin is known to regulate the body’s inflammation response, but until this study it wasn’t suspected of regulating angiogenesis. It’s possible that since the integrin only works on developing blood vessels and in cancer, disrupting its ability to form blood vessels could starve the tumor and stave off cancer."

The research team discovered that the integrin brought the endothelia, the inside part of a blood vessel, together to bind with vascular smooth muscle, the outer portion of a blood vessel. Blood vessels only work when both endothelia and vascular smooth muscle are bound together. Previous work on integrin alpha4beta1 showed that the protein worked in the immune system by binding with another molecule called VCAM, so the researchers next looked for evidence of VCAM in the vascular smooth muscle cells, called pericytes.

Indeed, Varner’s team found VCAM on the nascent blood vessel’s pericytes, but not in mature vessel pericytes. The two molecules, Varner discovered, work together to bring the endothelial cells together with the outer pericytes to create new intact blood vessels, with integrin as the lock and VCAM as the key. Drugs that inhibit either the integrin or the VCAM molecule prevented intact blood vessels from forming.

"When the integrin meets with VCAM, both cell types receive survival signals at this active stage of blood vessel development, which occurs mainly in tumors in adults," said Varner. "This was a chance discovery, which was exciting, and we think it may have important clinical significance."

In their current studies of breast cancer patients for the presence of the integrin and VCAM, "We want to know if the integrins predict aggressive breast cancer. If so, this could become a valuable, non-invasive diagnostic tool for cancer," said Varner.

In addition, knowing how blood vessels are finally assembled could help lead to effective ways to stop the proliferation of cancer cells by cutting off their nutrient supply, Varner added. Drs. Varner and Parker are currently in discussions with pharmaceutical companies to test integrin inhibitors in cancer clinical trials at the new Moores UCSD Cancer Center.

Varner’s colleagues in the study included Barbara Garmy-Susini, Hui Jin, Yuhong Zhu, Rou-Jia Sung and Rosa Hwang, all of UCSD.

Leslie Franz | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>