Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research points in new direction for cancer clues

11.02.2004


Team shows tumors can be triggered in normal cells by signals from nearby supporting cells



Like a detective combing the scene of a crime for clues, researchers often target their search for cancer causes in the cells known as epithelial cells. After all, it is these cells that most often become cancerous, so it makes sense to look for what goes wrong inside these cells.

However, a new report from a team of Vanderbilt-Ingram Cancer Center scientists demonstrates that tumors can develop from completely normal epithelial cells solely because of changes in signals from nearby supporting cells.


Writing in the Feb. 6 issue of Science, the team reports the dramatic development of precancerous prostate lesions and invasive cancers in the forestomachs of mice bred to eliminate a particular cell signaling pathway only in fibroblasts. These fibroblasts are supporting cells adjacent to the epithelial cells.

"The key finding is that we were able to show that a signaling pathway in the fibroblasts is important and can have a dramatic effect on epithelial cells in these animals," said Dr. Harold L. Moses, Benjamin F. Byrd Professor of Oncology, director of the Vanderbilt-Ingram Cancer Center, and director of the Frances Williams Preston Laboratories of the T.J. Martell Foundation for Leukemia, Cancer and AIDS Research. The paper results from a collaboration between Moses’ lab and the lab led by Dr. Eric G. Neilson, Hugh J. Morgan Professor and Chair of Medicine.

The Moses lab focuses on the role of transforming growth factor beta and its ability to either stimulate or inhibit cell growth depending upon the conditions. A standard approach to studying a particular protein or signaling pathway is to develop a genetically engineered "knock-out" mouse that does not express the particular protein in question. But TGF beta and its receptor are so critical to mammalian development, mice bred to eliminate this signaling pathway in all cells die as embryos.

To eliminate the TGF-beta pathway in only certain cells, the Moses lab in collaboration with Dr. Mark Magnuson’s and Dr. Christopher V.E. Wright’s laboratories developed a mouse in which the TGF-beta receptor included recognition points for a gene called Cre and its protein product. In cells where Cre is expressed, the TGF-beta receptor is selectively turned off.

The Neilson lab focuses on fibroblasts and had recently reported the potential of fibroblast-specific-protein 1 (FSP1) as a marker for cancer metastasis. This lab had developed a mouse that, under influence by FSP1, selectively expressed Cre in fibroblasts alone.

By crossing the two strains of mice, a new strain of animal was developed that expressed Cre only in the fibroblasts and so, in turn, eliminated TGF-beta expression only in the fibroblasts. The other cells in the mice were completely normal.

"We had developed the FSP1.cre mouse because we wanted to study selective gene interruptions in fibroblasts," Neilson said. "About the time our lab finished breeding our mouse, Hal and I realized that we would have an interesting experiment by crossing the two. At the time we decided to do the experiment, we weren’t thinking the mice would develop cancer."

But that is exactly what happened. The mice consistently developed precancerous lesions in the prostate and invasive squamous cell cancer in the forestomach (an organ in the mouse similar to the human esophagus).

Upon additional analysis, the researchers noted in the mouse forestomachs an elevation of a receptor for hepatocyte growth factor (HGF), which is known to be regulated by TGF-beta.

The findings suggest that when the TGF-beta pathway is active in the fibroblasts, they provide signals that keep growth of the neighboring epithelial cells in check; when the pathway is interrupted, cell growth is allowed to proceed unchecked, a result that may be related to an increase in HGF activity. "The seminal observation from crossing these mice is that you don’t need to have mutations in the epithelial cells for a carcinoma to result," Neilson said.

Dr. Neil Bhowmick, assistant professor of Urologic Surgery, lead author on the paper and a former member of the Moses lab, agreed.

"This really suggests new causes of cancer and targets for intervention," Bhowmick said. "We were looking at TGF-beta because that’s what we study. But it’s likely that there are other molecules in the stroma (supporting cells) that are important, too, and this opens the door for that research."

Bhowmick, who recently joined the Vanderbilt faculty, said that the project was of particular interest to him because it allowed him to collaborate with many other departments in the medical center. "The partnership was critical because without the mouse from the Neilson lab, we could never have made these observations."


Other co-authors on the paper were Anna Chytil, and Agnieszka E. Gorska of the department of Cancer Biology; David Plieth and Nancy Dumont, of the department of Medicine; and Scott Shappell and Kay Washington of the department of Pathology.

The work was supported by the National Institutes of Health (National Cancer Institute), the U.S. Department of Defense, and the T.J. Martell Foundation for Leukemia, Cancer and AIDS Research.

Cynthia Floyd Manley | EurekAlert!
Further information:
http://www.mc.vanderbilt.edu/reporter/

More articles from Health and Medicine:

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

nachricht Flexible sensors can detect movement in GI tract
11.10.2017 | Massachusetts Institute of Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Breaking: the first light from two neutron stars merging

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....

Im Focus: Smart sensors for efficient processes

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...

Im Focus: Cold molecules on collision course

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...

Im Focus: Shrinking the proton again!

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...

Im Focus: New nanomaterial can extract hydrogen fuel from seawater

Hybrid material converts more sunlight and can weather seawater's harsh conditions

It's possible to produce hydrogen to power fuel cells by extracting the gas from seawater, but the electricity required to do it makes the process costly. UCF...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Study suggests oysters offer hot spot for reducing nutrient pollution

17.10.2017 | Life Sciences

Breaking: the first light from two neutron stars merging

17.10.2017 | Physics and Astronomy

World first for reading digitally encoded synthetic molecules

17.10.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>