Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lower levels of key protein influence tumor growth in mice

02.06.2009
Tumors need a healthy supply of blood to grow and spread. Researchers at the Stanford University School of Medicine have identified a molecule that regulates blood vessel growth that is often found at less-than-normal levels in human tumors. Blocking the expression of the molecule, called PHD2, allows human cancer cells to grow more quickly when implanted into mice and increases the number of blood vessels feeding the tumor.

"It appears to be acting as a tumor suppressor by negatively controlling blood vessel formation," said cancer biologist Amato Giaccia, PhD, the Jack, Lulu and Sam Willson Professor and professor of radiation oncology. He and his colleagues are hopeful that targeting the downstream molecules activated when PHD2 levels are low may be an effective treatment for a variety of human cancers.

Giaccia is the senior author of the research, which will be published in the June 2 issue of the journal Cancer Cell. He is also a member of Stanford's Cancer Center.

The finding was particularly surprising because PHD2 was already known to play a less-direct role in blood vessel formation: that of destabilizing another important cancer-associated protein, HIF-1. HIF-1, which stimulates blood vessel development, is induced by the low oxygen levels found in many solid tumors. Although the HIF-1 molecule is rarely modified in human cancers, its levels are often elevated as compared to normal tissue. Giaccia and his colleagues wondered if the higher levels of HIF-1 could be explained by decreases in the level of PHD2.

The researchers measured PHD2 levels in several human tumor samples, including breast and colon cancers, and compared them with surrounding tissue. They found that, in many cancers, the tumors did have lower-than-normal levels of PHD2. They then inhibited the expression of PHD2 in a variety of human cancer cells in the lab, transplanted these cells into mice with compromised immune systems and examined the tumors that resulted. Those arising from cells in which PHD2 expression had been blocked grew more quickly and were more highly vascularized than the unmodified control cells.

Surprisingly, however, these effects of PHD2 inhibition were evident even in cells engineered not to express HIF-1. "Nobody expected this," said Giaccia. "It's always been thought that the major role of PHD2 was in regulating HIF-1 activity. But now we've learned that it seems to control tumor growth through blood vessel formation in a variety of different cell types on its own."

Upon further investigation, the researchers learned that blocking PHD2 expression increases the levels of two other important proteins involved in vessel formation: IL-8 and angiogenin. The researchers believe that blocking the activity of these proteins may be a good way to stunt tumor growth. "Prior to this study," said Giaccia, "it was unclear which of the many proteins involved in vessel growth, or angiogenesis, should be targeted. But now we know they play a predominant role in tumor growth."

He and his colleagues are planning to continue their studies in laboratory mice engineered to develop breast cancer. They will investigate whether a version of the mice lacking PHD2 expression develops more aggressive tumors, and whether blocking IL-8 or angiogenin slows tumor growth.

In addition to Giaccia, other Stanford researchers involved in the work include postdoctoral scholar Denise Chan, PhD; graduate student Tiara Kawahara; and associate professor of dermatology Howard Chang, MD, PhD. The study was funded by a Silicon Valley Community Fellowship, the National Cancer Institute and the National Institutes of Health.

The Stanford University School of Medicine consistently ranks among the nation's top 10 medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.

PRINT MEDIA CONTACT: Krista Conger at (650) 725-5371 (kristac@stanford.edu)
BROADCAST MEDIA CONTACT: M.A. Malone at (650) 723-6912 (mamalone@stanford.edu)

Krista Conger | EurekAlert!
Further information:
http://www.stanford.edu

More articles from Studies and Analyses:

nachricht WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf

nachricht First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

When corals eat plastics

24.05.2018 | Ecology, The Environment and Conservation

Surgery involving ultrasound energy found to treat high blood pressure

24.05.2018 | Medical Engineering

First chip-scale broadband optical system that can sense molecules in the mid-IR

24.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>