Nav: Home

A PoEM on breast cancer metastasis

August 28, 2019

When breast cancer cells spread through the body, they do so mainly through the lymph system that normally removes excess fluid and waste products from our tissues. Now, scientists from the group of Professor Massimiliano Mazzone (VIB-KU Leuven Center for Cancer Biology) identified a novel subset of immune cells, called Podoplanin-expressing macrophages (PoEMs), that change the tissues near a tumor in a way that promotes the spreading of cancer cells. Getting rid of these PoEMs in a mouse model strongly reduced the ability of breast cancer cells to move to other parts of the body.

Lymph highways for cancer cells

The lymphatic system drains excessive fluid and removes waste products from our tissues. Lymphatic vessels can also play a role in the spread of breast cancer. Growing tumors often put physical pressure on their environment, which makes these lymphatic vessels leaky and easier accessible for tumor cells.

The cancer cells take advantage of these leaks to move through the body and start growing tumors elsewhere, in a process called metastasis. Previous studies have shown that breast cancer cells prefer to move through the lymph system and that more lymphatic vessels near the tumor correlate with a more dire prognosis for patients.

Therefore, therapies that effectively tackle the development and growth of lymph vessels could reduce metastasis and therefore the death toll from mammary tumors, which remain virtually incurable when not detected on time.

PoEMs that promote metastasis

The development and growth of lymph vessels near tumors is sometimes supported by a certain type of immune cell. In this new study, Pawel Bieniasz-Krzywiec from the Mazzone team identified a subgroup of these cells, called Podoplanin-expressing macrophages (PoEMs).

But what is the importance of the presence of PoEMs in this specific environment? Prof. Mazzone explains: "PoEMs are characterized by a unique gene signature related to changes in the tumor's environment. Specifically, they are an excellent source of Collagen 1, which constitutes the supporting scaffold for growing lymphatic vessels. PoEMs also digest some parts of this environment. This liberates various growth factors that stimulate the formation of lymph vessels and gives rise to new routes for cancer cells dissemination."

The team further observed that PoEMs loosen up the connections between the cells that form the walls of the lymph vessels, which makes it easier for cancer cells to enter these highways. In mice, preventing PoEMs from 'environmental remodeling' highly decreased lymph node and distant organ metastasis.

Blocking PoEMs to fight cancer

These findings provide supportive evidence to targeting PoEMs in humans. With the help of clinicians and pathologists from KU Leuven and UZ Antwerpen, the researchers further tested their findings in human cancer samples. Pawel Bieniasz-Krzywiec provides more details: "On top of the mice results, human breast cancer sample testing revealed a positive correlation between the presence of PoEMs around tumor lymph vessels and lymph node involvement as well as organ metastasis. These observations pave the road towards the use of PoEM blockers in cancer therapy, specifically targeting the cancer-associated lymphatic vessels, without triggering lymphedema associated with current strategies."

From a broader perspective, the study highlights an emerging concept that properties of immune cells are inherently related to the specific environment they reside in. The study of Prof. Mazzone's team describes for the first time a subset of immune cells specifically associated with tumor lymphatics and promoting their growth.

"Our findings change the way we understand lymph vessel growth near tumors and will surely stimulate new and exciting research in the field," Prof. Mazzone concludes.

Podoplanin-expressing macrophages promote lymphangiogenesis and Lymphoinvasion in breast cancer, Mazzone et al., Cell Metabolism 2019


ERC Consolidator Grant (773208), Worldwide Cancer Research (13-1031), Fonds Wetenschappelijk Onderzoek (G087615N)

Questions from patients

A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.

VIB (the Flanders Institute for Biotechnology)

Related Science Articles:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.
Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.
Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.
Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.
World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.
PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.