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 New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

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: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>