Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genetically modified mice to visualize in vivo inflammation and metastasis

03.04.2012
The CNIO authors have developed mice in which lymph nodes that are going to be invaded by tumor cells emit light

One of the major routes of tumor cell dissemination to form metastasis at distant organs in the body is the lymphatic system. To study this process, still poorly understood, and to gain information on which tumors prefer this route for dissemination and how to block it, researchers of the Spanish National Cancer Research Center (CNIO), led by researcher Sagrario Ortega, have created transgenic mice in which, for the first time, the growth of the lymphatic vessels can be visualized in the whole animal, by a light-emitting reaction, as tumor progresses and forms metastasis.

The technique is so sensitive that it allows monitoring those lymph nodes that are going to be invaded by tumor cells. The work is published today in the journal PNAS (Proceedings of the National Academy of Sciences).

The normal physiological function of the lymphatic vessels is to collect fluid, molecules and cells from tissues and transport them to the blood stream. This system is essential for proper tissue drainage and its disfunction leads to fluid accumulation or lymphedema. The lymphatic system also participates in several diseases related to the immune response and inflammation and plays a very important role in the dissemination of tumor cells that, through the lymphatic vasculature reach first the sentinel lymph nodes and later distant organs to form metastasis.

The mice designed and created by the group of Sagrario Ortega, Head of the Transgenic Mice Unit of the CNIO, look completely normal at sight. But they carry additional genes that are expressed in the walls of the lymphatic vessels, under the control of the regulatory signals of Vegfr3, the first marker of lymphatic vessels identified. One of these genes is the one encoding a protein called luciferase, responsible of the light emitted by fireflies.

In the insect, the luciferase catalyzes the oxidation of its natural substrate, the luciferin, in a light emitting chemical reaction. Therefore in these mice, the lymphatic vessels emit light when the animals are injected with the totally innocuous substance luciferin. This light emission is captured in the dark using highly sensitive cameras.

The other gene that is expressed in these mice is the green fluorescent protein (GFP) that allows visualization of lymphatic vessels at the cellular level.

"The generation and characterization of these mice has been a great effort but certainly worthwhile" says Inés Martínez-Corral, first author in the PNAS publication and for whom this work has been her Doctoral Thesis"

What makes these mice very useful for the study of cancer and metastasis is that, in them, the proliferation of the lymphatic vessels -technically lymphangiogenesis-, a process that in the adult only takes place in pathological situations such as inflammation and tumors, can be directly visualized in the whole animal without invasive histological techniques.

Tumor cells send signals that induce proliferation of lymphatic vessels, not only at the periphery of the tumor but also in the lymph nodes facilitating the dissemination of tumor cells and the formation of metastasis, by a mechanism that is still poorly understood.

A NEW STEP TOWARDS THE DEVELOPMENT OF NEW THERAPIES

"These processes are detected in a very early stage in our mice, even before the lymph node invasion by tumor cells, by an increase in light emission and without need of histological techniques. These mice provide a unique tool for the study of inflammation and metastasis and for the development of new anti-metastatic therapies", explains Ortega.

For some tumors, such as melanoma or breast, the lymphatic system plays an important role in metastatic spread. But, in general, the connection between formation of new lymphatic vessels from pre-existing ones and tumor dissemination is poorly understood. This is why this technique is especially useful.

The new transgenic mice are already being used for several groups at the CNIO in search for markers that identify tumors that spread mostly through the lymphatics and to investigate how to block this process pharmacologically. One of the first tumors that are being studied using these mice is melanoma, in collaboration with the group of Maria S. Soengas, Director of the Molecular Pathology Program of the CNIO.

Juan J. Gómez | EurekAlert!
Further information:
http://www.cnio.es

More articles from Life Sciences:

nachricht A Fluttering Accordion
04.08.2015 | Friedrich-Schiller-Universität Jena

nachricht Molecular Spies to Fight Cancer - Procedure for improving tumor diagnosis successfully tested
03.08.2015 | Helmholtz-Zentrum Dresden-Rossendorf

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Greenhouse gases' millennia-long ocean legacy

Continuing current carbon dioxide (CO2) emission trends throughout this century and beyond would leave a legacy of heat and acidity in the deep ocean. These...

Im Focus: Glaciers melt faster than ever

Glacier decline in the first decade of the 21st century has reached a historical record, since the onset of direct observations. Glacier melt is a global phenomenon and will continue even without further climate change. This is shown in the latest study by the World Glacier Monitoring Service under the lead of the University of Zurich, Switzerland.

The World Glacier Monitoring Service, domiciled at the University of Zurich, has compiled worldwide data on glacier changes for more than 120 years. Together...

Im Focus: Quantum Matter Stuck in Unrest

Using ultracold atoms trapped in light crystals, scientists from the MPQ, LMU, and the Weizmann Institute observe a novel state of matter that never thermalizes.

What happens if one mixes cold and hot water? After some initial dynamics, one is left with lukewarm water—the system has thermalized to a new thermal...

Im Focus: On the crest of the wave: Electronics on a time scale shorter than a cycle of light

Physicists from Regensburg and Marburg, Germany have succeeded in taking a slow-motion movie of speeding electrons in a solid driven by a strong light wave. In the process, they have unraveled a novel quantum phenomenon, which will be reported in the forthcoming edition of Nature.

The advent of ever faster electronics featuring clock rates up to the multiple-gigahertz range has revolutionized our day-to-day life. Researchers and...

Im Focus: Superfast fluorescence sets new speed record

Plasmonic device has speed and efficiency to serve optical computers

Researchers have developed an ultrafast light-emitting device that can flip on and off 90 billion times a second and could form the basis of optical computing.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Success 4.0 – Is Your Company Fit for the Future? New Series of Events for Executives

04.08.2015 | Event News

3rd Euro Bio-inspired - International Conference and Exhibition on Bio-inspired Materials

23.07.2015 | Event News

Clash of Realities – International Conference on the Art, Technology and Theory of Digital Games

10.07.2015 | Event News

 
Latest News

Small tilt in magnets makes them viable memory chips

04.08.2015 | Information Technology

New Design Brings World’s First Solar Battery to Performance Milestone

04.08.2015 | Power and Electrical Engineering

Magnetism at Nanoscale

04.08.2015 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>