Lymphatic fluid takes detour

May 20, 2013 by Fabio Bergamin, ETH Zurich
Using an imaging process, scientists from ETH Zurich are able to render lymphatic vessels visible, including newly formed ones (left in the picture, microscopic image). Credit: Steven Proulx et al. / Biomaterials

When tumours metastasise, they can block lymphatic vessels, as researchers from ETH Zurich have discovered using a new method. The lymphatic fluid subsequently has to find a new path through the tissue. Such "detours" could well be the reason why metastasis misdiagnoses can occur in hospitals.

A alters the lymphatic system around it – and in a much more complex way than was previously assumed. Tumours are known to release messengers to trigger the formation of new . Researchers from ETH Zurich have now discovered that a metastatic tumour can also block lymphatic vessels completely.

The fact that the impact of tumours on the lymphatic system is so diverse underlines the importance of the in cancer and its spreading. Metastases form when break away from the original tumour and are washed into a lymph node with the lymphatic fluid, where they can metastasise. As a team of scientists headed by Michael Detmar, a professor at the Institute of , has now revealed, if this metastasis grows it can block the lymphatic flow to the corresponding lymph node. As a result, the lymphatic fluid needs to find a new path through the tissue to another lymph node, effectively taking a "detour".

Nano marker substance for lymphatic tissue

The ETH-Zurich scientists made this observation in experiments on mice using a relatively novel, non-invasive imaging technique called near , which involves injecting a fluorescent substance into the body that "glows" in the shortwave if stimulated with . Using an , the radiation can be recorded and thus the distribution of the marker substance observed. Thanks to one such new substance developed on a by Jean-Christophe Leroux, also a professor at the Institute of Pharmaceutical Sciences, it is now possible to display lymphatic vessels specifically with near infrared imaging for the first time.

To produce the nano marker substance, the researchers combined fluorescent dye molecules with a series of other comparatively large molecules with a precisely defined diameter. In tests conducted on mice, a molecule diameter of eight to ten nanometres proved ideal to render the lymphatic vessels visible. "These molecules are large enough to be transported in the lymphatic fluid yet small enough not to be absorbed by the body's own scavenger cells and transported into the bloodstream," explains Detmar.

Method with benefits

The dye becomes conspicuous by glowing brightly. "We can illuminate anatomical details with it that you couldn't see in the past, such as the tiny lymph valves in the lymphatic vessels," explains Detmar. Because, according to the research to date, the new substance is not toxic and can be excreted back out of the body, it is just the ticket for use in humans in future. Clinical trials are already in the pipeline.

Another advantage over alternative imaging techniques, such as positron emissions tomography (PET): near infrared imaging is much more straightforward. Instead of being reliant on the infrastructure of central hospitals, one day we will be able to use the method anywhere with the aid of portable infrared cameras, even in small medical practices.

Metastases misdiagnoses

According to Detmar, the ETH-Zurich scientists' observation that the lymphatic vessels can be blocked by metastases through to the lymph nodes will have a major impact on cancer medicine. In oncology, the general view is that a tumour that metastasises does so in so-called sentinel lymph nodes, the lymph node into which the lymphatic fluid is conducted from the tumour. In order to detect these sentinel in breast or skin cancer patients, for example, a doctor injects a dye into the tumour. The first lymph node into which this dye is transported is regarded as a sentinel lymph node. During the subsequent biopsy, an expert can determine whether it is a metastatic node.

However, the scientists' work now reveals that this method is not foolproof. After all, if a metastasis in a lymph node blocks the lymphatic flow and the fluid is redirected to another lymph node, as it stands the doctor examines the latter for metastases. If this lymph node is not metastatic, a misdiagnosis can occur, according to which the patient does not have any and thus does not receive the correct treatment. Detmar is convinced that near infrared imaging has a major advantage over conventional methods due to its high resolution: in many cases, the initial stages of the blocked vessels are visible with near infrared imaging.

Explore further: Evidence strengthens link between NSAIDs and reduced cancer metastasis

More information: Proulx, S. et al. Use of a PEG-conjugated bright near-infrared dye for functional imaging of rerouting of tumor lymphatic drainage after sentinel lymph node metastasis. Biomaterials, 2013, 34: 5128-5137. doi: 10.1016/j.biomaterials.2013.03.034

Related Stories

Evidence strengthens link between NSAIDs and reduced cancer metastasis

February 13, 2012
A new study reveals key factors that promote the spread of cancer to lymph nodes and provides a mechanism that explains how a common over-the-counter anti-inflammatory medication can reduce the spread of tumor cells through ...

Lymphoseek approved to help locate lymph nodes

March 13, 2013
(HealthDay)—The injected imaging drug Lymphoseek (technetium Tc 99m tilmanocept) has been approved by the U.S. Food and Drug Administration to help surgeons locate the lymph nodes among people with breast cancer or melanoma.

Tumor-activated protein promotes cancer spread

May 13, 2013
Researchers at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center report that cancers physically alter cells in the lymphatic system – a network of vessels that transports and ...

New signaling pathway linked to breast cancer metastasis

April 2, 2012
Lymph nodes help to fight off infections by producing immune cells and filtering foreign materials from the body, such as bacteria or cancer cells. Thus, one of the first places that cancer cells are found when they leave ...

Preschool within lymphatic vessels

August 9, 2012
Not only infants crawl. ETH researchers have shown that so-called dendritic cells, important cells of the immune system, use a similar mode of movement more often than previously assumed. The scientists used intravital microscopy ...

Genetically modified mice to visualize in vivo inflammation and metastasis

April 2, 2012
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 ...

Recommended for you

Scientists in Germany improve malaria drug production

February 21, 2018
Scientists in Germany who developed a new way to make a key malaria drug several years ago said Wednesday they have come up with a technique to make the process even more efficient, which should increase global access and ...

Products derived from plants offer potential as dual-targeting agents for experimental cerebral malaria

February 21, 2018
Malaria, a life-threatening disease usually caused when parasites from the Plasmodium family enter the bloodstream of a person bitten by a parasite-carrying mosquito, is a severe health threat globally, with 200 to 300 million ...

Early results from clinical trials not all they're cracked up to be, shows new research

February 21, 2018
When people are suffering from a chronic medical condition, they may place their hope on treatments in clinical trials that show early positive results. However, these results may be grossly exaggerated in more than 1 in ...

Spare parts from small parts: Novel scaffolds to grow muscle

February 20, 2018
Australian biomedical engineers have successfully produced a 3D material that mimics nature to transform cells into muscle.

Clues to obesity's roots found in brain's quality control process

February 20, 2018
Deep in the middle of our heads lies a tiny nub of nerve cells that play a key role in how hungry we feel, how much we eat, and how much weight we gain.

Study looks at how newly discovered gene helps grow blood vessels

February 19, 2018
A new study published today found that a newly discovered gene helps grow blood vessels when it senses inadequate blood flow to tissues.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.