Lung cancer is the most common cause of cancer death and an area where novel therapies to block metastasis are desperately needed, according to first author Mark M. Fuster, M.D., assistant professor in the Division of Pulmonary and Critical Care Medicine in UCSD’s Department of Medicine. Solid tumors need a network of blood vessels, or vasculature, in order to grow, and this vasculature drives metastasis. The research team, led by the paper’s principal investigator Jeffrey D. Esko, Ph.D., professor of Cellular and Molecular Medicine at UCSD, showed that modifying the action of heparan sulfate uniquely impacted the tumor vasculature, and in doing so, altered the growth rate of tumors prepared from lung carcinoma cells in the mice.
"We theorized that by targeting the sugar, heparan sulfate, we could affect angiogenesis, which is the formation of new blood vessels," said Fuster. "In cancer, angiogenesis sustains growth as well as metastasis of tumors. An important finding was that, not only could we inhibit the growth of tumors in these mice, but that other systems that rely on endothelial growth, such as the reproductive system and wound healing, remained robust."
Studying mouse models with a genetic alteration in an important sugar-modifying enzyme (Ndst1), the researchers saw a marked decrease in the growth of experimental carcinomas. The Ndst1 enzyme is responsible for modifying the molecular structure of a sugar called heparan sulfate. In endothelial cells, this sugar facilitates the action of several important vascular growth factors that support angiogenesis.
An antibody drug called Avastin, produced by Genentech, has been shown to block a major pro-angiogenesis molecule called vascular endothelial growth factor (VEGF), thus inhibiting the growth of vasculature. The drug has been used along with chemotherapy in humans to successfully inhibit the growth of tumors in colon and lung cancers.
"If novel drugs can be developed to target tumor heparan sulfate, we might be able to make a leap in cancer-fighting therapies, because several molecules critical to tumor endothelial growth also bind to heparan sulfate," Fuster said. "Altering this binding would allow for suppression of a broader array of the tumor ‘fuels’ for angiogenesis, without a major effect on normal vascular function."
The researchers hope to develop novel therapies by inhibiting endothelial heparan sulfate in the tumor environment. An example would be developing small-molecule inhibitors of Ndst1. By affecting a broad array of molecules – such as VEGF, fibroblast growth factor, platelet-derived growth factor, or others that impact angiogenesis in a variety of carcinomas – this therapy could be used to inhibit cancer growth and metastasis with fewer side effects.
Debra Kain | EurekAlert!
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research