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
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!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy