Featured Research

from universities, journals, and other organizations

Dual-action protein better restricts blood vessel formation

Date:
August 12, 2011
Source:
Stanford School of Engineering
Summary:
Bioengineers have created a single protein able to target two different chemical receptors at the same time, yielding a promising new direction in the development of cancer treatments and other biomedical applications.

Cancer needs blood. In fact, some cancer medications work solely to slow or prevent cancer cells from creating new capillaries, choking off their much-needed blood and nutrient supply to halt the growth of tumors.

In a paper published online Aug. 8 in the Proceedings of the National Academy of Sciences, researchers at Stanford University describe the creation of a new type of engineered protein that is significantly more effective at preventing the formation of blood vessels by targeting not one, but two of the chemical receptors that control the creation of new capillaries -- a process known as angiogenesis. The study shows that the new protein blocks both receptors.

"Chemical receptors and their protein ligands control many cellular functions, but the protein must fit the receptor exactly. It's like a molecular jigsaw puzzle," said lead researcher Jennifer Cochran, PhD, assistant professor of bioengineering. "When the right proteins come along and engage their matching receptors, things begin to happen at the cellular level. In this case, we looked at the chemical signaling and cellular machinery responsible for producing new blood vessels."

Existing cancer treatments block the activity of specific receptors that control capillary creation. Some of these drugs act like a cork in a bottle, occupying the receptor and thus preventing capillary-inducing proteins from activating cell signaling and biochemical processes, while others attach to the capillary-inducing proteins and shield the receptor from them.

Complicating matters for cancer researchers, however, is the fact that angiogenesis is often controlled by multiple receptors working together. "Cell-signaling pathways are analogous to a safe-deposit box requiring many keys to open," said Cochran.

In such situations, receptors work in tandem, communicating back and forth in a chemical collaboration known as cross-talk. Current anti-angiogenesis therapies, however, are able to target only single receptors. Thus, significantly limiting capillary growth requires blocking more than one receptor.

Cochran's team -- including postdoctoral scholars Niv Papo, PhD, Adam Silverman, PhD, and Jennifer Lahti, PhD, who was a graduate student at the time of the research -- identified likely pairs of collaborating receptors. They knew from a body of earlier research that there was significant cross-talk between two specific angiogenic receptors. Their goal was to create a single protein that could block both.

First, the team selected a protein that bonds with one of the receptors. Using it as a molecular "scaffold" they affixed, or substituted, a new section that could bond with the second receptor, all without altering the original function or the physical structure of the larger scaffold protein. They succeeded; their new protein blocks both receptors.

When delivered in a nutrient-rich matrix and implanted in mice, the Stanford protein showed dramatic ability to halt the creation of new capillaries. "Samples treated with our dual-action protein have minimal blood vessel formation, similar to a sample in which angiogenic factors are absent," Cochran said. "Importantly, this engineered protein more strongly inhibits angiogenic processes compared to single-receptor blockers."

Some researchers have suggested that the same result might be accomplished more easily with a cocktail of drugs, each targeting a specific receptor. Cochran acknowledged the feasibility of such approaches, but pointed out that each drug in the cocktail would require clinical trials and the approval of the U.S. Food and Drug Administration. The new protein could be the basis for one drug.

"This is a major advantage of two-in-one molecules," said Cochran. "A single FDA-approval process could possibly shave years off the development process, and there are obvious cost benefits to manufacturing only one drug instead of several. In addition, using state-of-the-art protein engineering methods that have been developed within the past decade or so, such molecules could be engineered for optimal therapeutic benefit while reducing unwanted side effects"

Beyond cancer, Cochran noted, the prevention of angiogenesis could prove helpful in the treatment of diseases such as macular degeneration, one form of which can lead to visual impairment or even blindness when unchecked capillaries grow in the retina.

As for the scaffolding approach, she said she sees a research strategy that might be applied to develop new, multifunctional proteins that work in other biomedical applications, from diagnostics and immunotherapy to tissue repair.

"All the attention being accorded dual-action proteins is warranted," Cochran said. "Sometimes, two are better than one."

This research was funded by an American Cancer Society Research Scholar Grant.


Story Source:

The above story is based on materials provided by Stanford School of Engineering. The original article was written by Andrew Myers. Note: Materials may be edited for content and length.


Journal Reference:

  1. N. Papo, A. P. Silverman, J. L. Lahti, J. R. Cochran. Antagonistic VEGF variants engineered to simultaneously bind to and inhibit VEGFR2 and v3 integrin. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1016635108

Cite This Page:

Stanford School of Engineering. "Dual-action protein better restricts blood vessel formation." ScienceDaily. ScienceDaily, 12 August 2011. <www.sciencedaily.com/releases/2011/08/110811162839.htm>.
Stanford School of Engineering. (2011, August 12). Dual-action protein better restricts blood vessel formation. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2011/08/110811162839.htm
Stanford School of Engineering. "Dual-action protein better restricts blood vessel formation." ScienceDaily. www.sciencedaily.com/releases/2011/08/110811162839.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
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:
from the past week

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