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 NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

nachricht High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University

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: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>