Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Study offers new insights into angiogenesis inhibitors


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:

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

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: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Physicists made crystal lattice from polaritons

20.03.2018 | Physics and Astronomy

Mars' oceans formed early, possibly aided by massive volcanic eruptions

20.03.2018 | Physics and Astronomy

Thawing permafrost produces more methane than expected

20.03.2018 | Earth Sciences

Science & Research
Overview of more VideoLinks >>>