Featured Research

from universities, journals, and other organizations

Cholesterol inhibitors block lymphatic vessel growth

Date:
September 3, 2012
Source:
ETH Zürich
Summary:
One of the world's top selling drugs potentially also acts against the growth of new lymphatic vessels, with potential implications for cancer therapy. This surprising finding was brought forward by researchers with their newly developed three-dimensional cell culture system.

Human lymphatic endothelial cells on a microscopic micro carrier bead build so-called sprouts (microscopic image).
Credit: Martin Schulz / ETH Zurich / PNAS

One of the world's top selling drugs potentially also acts against the growth of new lymphatic vessels, with potential implications for cancer therapy. This surprising finding was brought forward by researchers at ETH Zurich with their newly developed three-dimensional cell culture system.

Related Articles


Researchers of the Institute of Pharmaceutical Sciences at ETH Zurich and the University of California Berkeley have made an unexpected discovery. Their search for novel pharmaceuticals that might prevent the generation of tumour metastases identified a well-known drug class: the statins. These cholesterol lowering compounds are standardly used to treat patients with cardiovascular disease to prevent the progression of atherosclerosis. Statins are among the most widely prescribed drugs worldwide.

Scientists led by Michael Detmar, Professor at the ETH Zurich Institute of Pharmaceutical Sciences of Pharmacogenomics, made this discovery with a newly developed cell culture system that allows compound screening for modulators of lymphatic vessel expansion. Lymphatic vessel growth is contributing to the dissemination of tumour cells in cancer patients and also the rejection of transplanted organs by the recipient's immune system. For their screening system, the researchers coated lymphatic endothelial cells from human skin onto microscopic micro carrier beads consisting of a natural polymer and encapsulated them in a tumour environment mimicking hydrogel. When stimulated with growth factors, the lymphatic endothelial cells started to build so-called sprouts, the first step for the formation of new lymphatic vessels.

Automated cell culture in 3D

For distinction to common cell culture methods, which consist of a two-dimensional cell layer in a plane cell culture dish, the researchers called their micro carrier bead system a three-dimensional system that enabled them to test over 1000 small chemical compounds.

"We were able to screen such a high number of substances because we succeeded in automating this process," explains Postdoc Martin Schulz, the first author of the respective study published in the Proceedings of the National Academy of Sciences. For this work, the researchers utilised an automated screening microscope at the light microscopy centre of ETH Zurich. This approach resulted in over 100'000 high-resolution images of the cell-coated micro beads that visualise the development of sprouts. The sprout number was determined by an algorithm developed especially for this study. "Manual analysis would allow a throughput of maybe ten compounds, but impossibly 1000," Schulz states.

System might allow reduction of animal experiments

By utilising known substances that inhibit lymphatic vessel growth, the researchers demonstrated that the results of their 3D-system are in closer agreement with animal experiments than commonly used cell culture test systems. "Our system thereby offers a better predictability," concludes Michael Detmar. "And in contrast to animal experiments, we are able to directly assess the response in human cells," adds Martin Schulz. The researchers are convinced that the number of animal experiments can be reduced with such a 3D-system, in particular with regard to the pharmacological testing of large numbers of chemical substances.

The so-called screening of over 1000 substances resulted in around 30 compounds that inhibit lymphatic vessel growth. Among several identified pharmaceuticals that were not known to convey this effect, two were investigated in more detail. One of the two -- as earlier mentioned -- belongs to the drug class of statins. Subsequently, the researchers confirmed the inhibitory effect of statins also in mice.

No suitable medicine available

The researchers consider it possible that statins in the future might not only be administered to patients with cardiovascular disease, but also to cancer patients. Many cancers spread over the body via lymphatic vessels, as has been known for some time -- also based on research in the group of Michael Detmar among others. Some tumours are known to secret mediators that induce the growth of lymphatic vessels towards the tumour. Therefore, clinical oncology has an interest in drugs that inhibit this growth. "So far, there are no reliable treatments available in the clinics," elaborates Detmar.

"In the future, one might imagine to prophylactically treat high risk cancer patients with statins to prevent developing tumours from metastasizing," says Detmar. Because of their extensive medical evaluation and market approval for other diseases, these drugs would require repurposing by the regulatory authorities for the application as inhibitors of lymphatic vessel growth. This process would be significantly easier than the approval of a new drug. However, according to Detmar, it is imperative to first investigate whether the commonly applied statin dosages are sufficient to reduce growth of lymphatic vessels in humans.


Story Source:

The above story is based on materials provided by ETH Zürich. Note: Materials may be edited for content and length.


Journal Reference:

  1. Martin Michael Peter Schulz, Felix Reisen, Silvana Zgraggen, Stephanie Fischer, Don Yuen, Gyeong Jin Kang, Lu Chen, Gisbert Schneider, and Michael Detmar. Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1206036109

Cite This Page:

ETH Zürich. "Cholesterol inhibitors block lymphatic vessel growth." ScienceDaily. ScienceDaily, 3 September 2012. <www.sciencedaily.com/releases/2012/09/120903221052.htm>.
ETH Zürich. (2012, September 3). Cholesterol inhibitors block lymphatic vessel growth. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2012/09/120903221052.htm
ETH Zürich. "Cholesterol inhibitors block lymphatic vessel growth." ScienceDaily. www.sciencedaily.com/releases/2012/09/120903221052.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) — The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) — An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
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