Featured Research

from universities, journals, and other organizations

Scientists aim to kill lung tumors

Date:
May 4, 2012
Source:
Max-Planck-Gesellschaft
Summary:
Enzyme regulates the division of tumor cells and blood vessel growth in the cancer tissue.

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.
Credit: MPI for Heart and Lung Research

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

Related Articles


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. 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.


Story Source:

The above story is based on materials provided by Max-Planck-Gesellschaft. Note: Materials may be edited for content and length.


Journal Reference:

  1. S S Pullamsetti, G A Banat, A Schmall, M Szibor, D Pomagruk, J Hänze, E Kolosionek, J Wilhelm, T Braun, F Grimminger, W Seeger, R T Schermuly, R Savai. Phosphodiesterase-4 promotes proliferation and angiogenesis of lung cancer by crosstalk with HIF. Oncogene, 2012; DOI: 10.1038/onc.2012.136

Cite This Page:

Max-Planck-Gesellschaft. "Scientists aim to kill lung tumors." ScienceDaily. ScienceDaily, 4 May 2012. <www.sciencedaily.com/releases/2012/05/120504135806.htm>.
Max-Planck-Gesellschaft. (2012, May 4). Scientists aim to kill lung tumors. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2012/05/120504135806.htm
Max-Planck-Gesellschaft. "Scientists aim to kill lung tumors." ScienceDaily. www.sciencedaily.com/releases/2012/05/120504135806.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) — It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) — More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) — In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) — The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins