Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study offers new insights into angiogenesis inhibitors

14.04.2003


In working to halt the overgrowth of blood vessels that feed cancerous tumors, the antiangiogenic molecules endostatin and tumstatin take two distinct and very different tactics, according to a study in the April 15 issue of the Proceedings of the National Academy of Sciences (PNAS).



These findings, which currently appear on-line, suggest for the first time that these two agents combined may prove more effective in battling cancer than either one used separately.

"Just as aspirin, acetaminophen and ibuprofen each work in different ways to relieve pain, it now appears that endogenous inhibitors like endostatin and tumstatin work in different ways to halt angiogenesis," explains the study’s senior author Raghu Kalluri, Ph.D., of the Center for Matrix Biology at Beth Israel Deaconess Medical Center (BIDMC). "These findings may help us to be more informed in the ways we use these molecules as potential drug candidates in the future."


Angiogenesis has been the focus of attention among cancer researchers for more than 30 years. The angiogenesis process takes place when a single layer of endothelial cells – which line the inside of the small blood vessels – break off from the vessels’ membrane and develop into new capillaries. In a number of diseases – including psoriasis, rheumatoid arthritis and diabetic retinopathy, as well as cancer – it is the unchecked growth of these capillaries that contributes to disease pathogenesis.

Over the years, scientists have identified a number of endogenous protein fragments which can put a halt to this process. Known as endogenous angiogenesis inhibitors, these include endostatin and tumstatin. Subsequent investigations have shown that these angiogenesis inhibitors might function by binding to a group of cell surface associated molecules known as integrins.

In this new study, Kalluri and his colleagues discovered that these two inhibitory molecules were binding to two separate and distinct integrins – endostatin to a5b1 integrin and tumstatin to aVb3 integrin – thereby achieving the same end effect of inhibiting angiogenesis, but by diverse mechanisms.

"While human endostatin targets the endothelial cells’ migratory abilities, human tumstatin prevents endothelial cells from proliferating," says Kalluri, who is an associate professor of medicine at Harvard Medical School. "These two different approaches lead to the same outcome – halting the outgrowth of the blood vessels and inhibition of tumor growth."

With this discovery, he adds, clinicians may be able to use these molecules in a more targeted fashion. "In order for endostatin to work, it has to be targeting tumors with the a5b1 positive tumor vasculature. Likewise, tumstatin must target tumors with aVb3 positive tumor vasculature," he explains. "Future clinical trials of these antiangiogenic therapies may benefit by building in these considerations."

"This is a very important piece of work," notes Judah Folkman, M.D., of Children’s Hospital Boston and Harvard Medical School, in whose laboratory endostatin was first discovered with Michael O’Reilly in 1997. "This paper shows an emerging set of proteins in the body which guard against abnormal angiogenesis, similar to the set of proteins that guard against blood clotting." This new finding, he adds, "suggests that because these two proteins inhibit angiogenesis by two separate pathways, they could eventually be used together for the treatment of cancer."

Study co-authors include Beth Israel Deaconess Medical Center researchers Akulapalli Sudhakar, Ph.D., Hikaru Sugimoto, M.D., Ph.D., Changqing Yang, M.D., Ph.D., Julie Lively, Ph.D., and Michael Zeisberg, M.D.


This study was funded by grants from the National Institutes of Health and funds from the Program in Matrix Biology at BIDMC. BIDMC owns patent rights to human tumstatin, which are exclusively licensed to Ilex Oncology, Inc. Raghu Kalluri and BIDMC hold equity in Ilex.

Beth Israel Deaconess Medical Center is a major patient care, research and teaching affiliate of Harvard Medical School and a founding member of CareGroup Healthcare System. Beth Israel Deaconess is the third largest recipient of National Institutes of Health research funding among independent U.S. teaching hospitals.

Bonnie Prescott | EurekAlert!
Further information:
http://www.bidmc.harvard.edu/

More articles from Health and Medicine:

nachricht Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

nachricht What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

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

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>