Featured Research

from universities, journals, and other organizations

Culprit behind unchecked angiogenesis identified

Date:
March 29, 2012
Source:
Max-Planck-Gesellschaft
Summary:
Researchers have unraveled a critical regulatory mechanism controlling blood vessel growth that might help solve drug resistance problems in the future.

This image shows growing blood vessels in the retina of a mouse. Vessels grow from the center to the outer parts of un-supplied tissue.
Credit: MPI for Molecular Biomedicine.

Max Planck researchers have unraveled a critical regulatory mechanism controlling blood vessel growth that might help solve drug resistance problems in the future.

Related Articles


Angiogenesis, the growth of new blood vessels, is a complex process during which different signalling proteins interact with each other in a highly coordinated fashion. The growth factor VEGF and the Notch signalling pathway both play important roles in this process. VEGF promotes vessel growth by binding to its receptor, VEGFR2, while the Notch signalling pathway acts like a switch capable of suppressing angiogenesis. Until recently, scientists had assumed that Notch cancels the effects of VEGF through the downregulation of VEGFR2. Now, researchers at the Max Planck Institute for Molecular Biomedicine and the Westphalian Wilhelms-University in Mόnster, Germany, were able to demonstrate that defective Notch signalling enables strong and deregulated vessel growth even when VEGF or VEGFR2 are inhibited.

In this case, a different VEGF family receptor, VEGFR3, is strongly upregulated, promoting angiogenesis. "This finding might help explain drug resistance issues in certain types of cancer therapy and could become the basis for novel treatment strategies," suggests Ralf Adams, MPI's Executive Director and Chair of the Department of Tissue Biology and Morphogenesis.

An extensively branched network of blood vessels provides every organ of the body with nutrients and removes harmful metabolic waste products from tissues. Growth of this vascular system is essential for development and wound healing processes. Uncontrolled angiogenesis contributes to diseases like hemangiomas, the sponge-like overgrowth of blood vessels in the skin, or retinopathies impairing the eyesight of diabetic and elderly individuals. In cancer therapy, inhibition of angiogenesis is used to starve tumours and prevent the metastatic spread of cancer cells via the circulation. At present, this is most frequently done by targeting VEGF or its receptor VEGFR2. When their oxygen supply becomes inadequate, tissues begin to release VEGF, which binds to VEGFR2, activating the receptor and thereby triggering vessel growth. Thus, the formation of new blood vessels can be blocked by inhibiting VEGF or VEGFR2. Unfortunately, existing treatments are inadequate and, for reasons that are not yet known, some patients respond poorly or not at all to VEGF/VEGFR2 inhibition.

Now, Rui Benedito, a postdoctoral research fellow in Adams' Department, has demonstrated that inhibition of the Notch pathway in blood vessels of the mouse eye permits strong and deregulated vessel growth even when VEGF or VEGFR2 are inhibited. "It turns out that another VEGF family receptor, VEGFR3, takes over, promoting the formation of new blood vessels," explains Benedito. VEGFR3 is strongly upregulated in blood vessels in the absence of Notch and is active even without growth signals from the surrounding tissues.

"What we need to do now is confirm whether VEGFR3 and other Notch-regulated signals are in fact capable of promoting VEGF-independent vessel growth in eye disease or cancer not only in mice but also in humans," explains Adams. "It might become possible to predict whether patients, depending on their vascular Notch activation status, are going to respond to VEGF or VEGFR2 inhibition. This would allow physicians to choose alternative therapies if necessary. Here, too, collaboration between MPI, the medical faculty, and the University of Mόnster is essential: "Our work is strongly benefitting from the excellent support provided by the University."


Story Source:

The above story is based on materials provided by Max-Planck-Gesellschaft. Note: Materials may be edited for content and length.


Journal Reference:

  1. Rui Benedito, Susana F. Rocha, Marina Woeste, Martin Zamykal, Freddy Radtke, Oriol Casanovas, Antonio Duarte, Bronislaw Pytowski, Ralf H. Adams. Notch-dependent VEGFR3 upregulation allows angiogenesis without VEGF–VEGFR2 signalling. Nature, 2012; DOI: 10.1038/nature10908

Cite This Page:

Max-Planck-Gesellschaft. "Culprit behind unchecked angiogenesis identified." ScienceDaily. ScienceDaily, 29 March 2012. <www.sciencedaily.com/releases/2012/03/120329101625.htm>.
Max-Planck-Gesellschaft. (2012, March 29). Culprit behind unchecked angiogenesis identified. ScienceDaily. Retrieved December 17, 2014 from www.sciencedaily.com/releases/2012/03/120329101625.htm
Max-Planck-Gesellschaft. "Culprit behind unchecked angiogenesis identified." ScienceDaily. www.sciencedaily.com/releases/2012/03/120329101625.htm (accessed December 17, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, December 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) — Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) — Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Flu Outbreak Closing Schools in Ohio

Flu Outbreak Closing Schools in Ohio

AP (Dec. 17, 2014) — A wave of flu illnesses has forced some Ohio schools to shut down over the past week. State officials confirmed one pediatric flu-related death, a 15-year-old girl in southern Ohio. (Dec. 17) Video provided by AP
Powered by NewsLook.com
Yoga Could Be As Beneficial For The Heart As Walking, Biking

Yoga Could Be As Beneficial For The Heart As Walking, Biking

Newsy (Dec. 17, 2014) — Yoga can help your weight, blood pressure, cholesterol and heart just as much as biking and walking does, a new study suggests. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins