Navigation Links
Dual-action protein developed at Stanford better restricts blood vessel formation

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.

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."


Contact: Andrew Myers
Stanford School of Engineering

Related biology news :

1. York U researchers zero in on protein that may help treat obesity, diabetes
2. Good prion-like proteins boost immune response, UT Southwestern scientists report
3. Genome of CHO-K1 provides new insights into optimization of biopharmaceutical protein production
4. 1st large-scale map of a plants protein network addresses evolution, disease process
5. Caltech researchers increase the potency of HIV-battling proteins
6. Software helps synthetic biologists customize protein production
7. Bacterial attack strategy uses special delivery of toxic proteins
8. Biologists discover an evening protein complex that regulates plant growth
9. Higher-protein diets can improve appetite control and satiety
10. Unnatural chemical allows Salk researchers to watch protein action in brain cells
11. A chaperone system guides tail-anchored membrane proteins to their destined membrane
Post Your Comments:
(Date:11/10/2015)... NEW YORK , Nov. 10, 2015 /PRNewswire/ ... refers to behavioral biometrics that helps to identify ... prevent fraud. Signature is considered as the secure ... for the identification of a particular individual because ... offers more accurate results especially when dynamic signature ...
(Date:11/9/2015)... Calif. , Nov. 9, 2015  Synaptics Inc. ... interface solutions, today announced broader entry into the automotive ... solutions that match the pace of consumer electronics human ... biometric sensors are ideal for the automotive industry and ... Europe , ...
(Date:11/2/2015)... , Nov. 2, 2015  SRI International has been ... provide preclinical development services to the National Cancer Institute ... will provide scientific expertise, modern testing and support facilities, ... preclinical pharmacology and toxicology studies to evaluate potential cancer ... The PREVENT Cancer Drug Development Program is an ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... November 24, 2015 --> ... research report "Oligonucleotide Synthesis Market by Product & Services ... Synthesis, Diagnostic, DNA, RNAi), End-User (Research, Pharmaceutical & Biotech, ... MarketsandMarkets, the market is expected to reach USD 1,918.6 ... at a CAGR of 10.1% during the forecast period. ...
(Date:11/24/2015)... ... ... The Academy of Model Aeronautics (AMA), led by its Executive Council, has officially ... to represent the First–Person View (FPV) racing community. , FPV racing has exploded in ... racing and several new model aviation pilots have joined the community because of their ...
(Date:11/24/2015)... ALBANY, New York , November 24, 2015 /PRNewswire/ ... According to a recent market research report released by ... is projected to expand at a CAGR of 17.5% ... titled "Non-invasive Prenatal Testing Market - Global Industry Analysis, ... 2022", estimates the global non-invasive prenatal testing market to ...
(Date:11/24/2015)... Nov. 24, 2015 /PRNewswire/ - Aeterna Zentaris Inc. ... that the remaining 11,000 post-share consolidation (or 1,100,000 ... (the "Series B Warrants") subject to the previously ... November 23, 2015, which will result in the ... effect to the issuance of such shares, there ...
Breaking Biology Technology: