Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists aim to starve lung tumours

07.05.2012
Enzyme regulates the division of tumour cells and blood vessel growth in the cancer tissue

Lung cancer is the leading cause of cancer death throughout the world. Standard treatment methods do not usually result in long-term recovery. In addition to the proliferation of the tumour cells, the growth of blood vessels controls tumors development.



Formation of PDE4 in oxygen-deficient lung tumour cells. Lung cells produce PDE4 (stained green: left) even if their oxygen content is normal. More PDE4 is produced (right) if they are oxygen-deficient (hypoxia). The cell nuclei are stained blue. © Max Planck Institute for Heart and Lung Research

The blood vessel growth is controlled by several signalling molecules. Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim and Justus Liebig University Giessen have discovered a molecule that plays a key role in this process. They succeeded in reducing tumour growth in their experiments by blocking the phosphodiesterase PDE4.

Lung cancer mainly affects smokers; however the disease can also be caused by contact with carcinogenic substances like asbestos. Chemotherapy or radiotherapy often prove insufficient in treating the disease. Hence, scientists are engaged in an intensive search for ways of halting the growth of lung tumours. The blood vessels that supply the tumour with nutrients offer a potential point of attack.

New blood vessels form to ensure an adequate supply of nutrients to the growing tumour. The growing tissue is immediately penetrated by blood vessels. The growth of the blood vessels is regulated by the tumour cells using a complex signal cascade, which is triggered initially by a low oxygen content (hypoxia) in the tumour tissue. “This state, which is known as hypoxia prompts the activation of around 100 genes in the tumour cells,” explains Rajkumar Savai, research group leader at the Max Planck institute. “In addition to the growth of blood vessels, hypoxia also stimulates the proliferation of lung cancer cells.” Three molecules play a particularly important role in this process. The activation of the genes at the beginning of the cascade is triggered by the transcription factor HIF and a messenger molecule, cAMP, is involved again at the end of the cascade. The researchers examined the third molecule that acts as a link between these two molecules in detail.

The molecule in question is a phosphodiesterase, PDE4. The scientists from Bad Nauheim and Giessen were able to demonstrate in their study that various sections of PDE4 have binding sites for HIF.

The researchers then tested the influence of a PDE4 blockade on the cells from ten different cell lines, which are characteristic of around 80 percent of lung cancers, in the laboratory. The rate of cell division in the cells treated with a PDE4 inhibitor was significantly lower and the HIF level also declined as a result.

The effect in the tumour bearing mice was particularly obvious. To observe this, the Max Planck researchers implanted a human tumour cell line under the skin of nude mice and treated the animals with the phosphodiesterase 4 inhibitor. Tumour growth in these animals declined by around 50 percent. “Our microscopic analysis revealed that the blood vessel growth in the tumours of the mice that had been treated with the inhibitor was significantly reduced. We also observed indicators of decelerated cell division in the tumour cells. Overall, the tumour growth was strongly curbed.”

Werner Seeger, Director of the MPI and Medical Director of the JLU University Hospital Giessen, reports: “We were able to show that PDE4 plays an important regulation function in cell division in lung tumours and in the development of blood vessels in cancer. Therefore, we hope that we have found a starting point for the development of a treatment here.” In the view of tumour specialist Friedrich Grimminger, Chairman of the Department of Medical Oncology in Giessen, it may be possible in future to combine the inhibition of PDE4 with traditional radiotherapy or chemotherapy. In this way, the effect of the traditional treatment measures could be reinforced and patient prognoses may improve as a result. However, further laboratory studies are required before clinical tests can be carried out.

Contacts

Dr. Rajkumar Savai
Max Planck Institute for Heart and Lung Research
Phone: +49 60 3270-5313
Fax: +49 60 3270-5211
Email: rajkumar.savai@­innere.med.uni-giessen.de
Dr. Matthias Heil
Max Planck Institute for Heart and Lung Research
Phone: +49 6032 705-1705
Fax: +49 6032 705-1704
Email: matthias.heil@­mpi-bn.mpg.de
Original publication
S. Pullamsetti, G. Banat, A. Schmall, M. Szibor, D. Pomagruk, J. Hänze, E. Kolosionek, J. Wilhelm, T. Braun, F. Grimminger, W. Seeger, R. Schermuly, R. Savai
Phosphodiesterase-4 promotes proliferation and angiogenesis of lung cancer by crosstalk with HIF.

Oncogene (2012). doi:10.1038/onc.2012.136

Dr. Rajkumar Savai | EurekAlert!
Further information:
http://www.mpg.de/5763400/lung_tumour_starvation

More articles from Life Sciences:

nachricht New way to look at cell membranes could change the way we study disease
19.11.2018 | University of Oxford

nachricht Controlling organ growth with light
19.11.2018 | European Molecular Biology Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

New materials: Growing polymer pelts

19.11.2018 | Materials Sciences

Earthquake researchers finalists for supercomputing prize

19.11.2018 | Information Technology

Controlling organ growth with light

19.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>