Nav: Home

Interactions between cancer cells and fibroblasts promote metastasis

March 23, 2020

In order to colonize other organs and grow into metastases, tumor cells that detach from the parent tumor need to manipulate their new microenvironment and create a 'metastatic niche'. Scientists from the German Cancer Research Center and the Heidelberg Institute for Stem Cell Technology and Experimental Medicine* have now discovered that some cancer cells stimulate connective tissue cells in their environment to release transmitters that promote metastasis. This discovery plays a key role in better understanding how these dangerous metastases arise.

If cancer cells detach from a tumor and move around the body, they are entering enemy territory. Many detached cancer cells do actually die before they manage to colonize other tissues and form metastases, because the body's immune system is geared toward protecting healthy tissue from intruders of all kinds. Moreover, these migrant cancer cells can only survive if they manage to manipulate the cells in their new environment to create a metastatic niche that helps the migrant cancer cells survive.

Thordur Oskarsson and his team at the German Cancer Research Center (DKFZ) and at the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH) are investigating how this metastatic niche arises. The scientists have now discovered both in cell cultures and in mice that some particularly aggressive breast cancer cells induce a situation similar to inflammation in lung tissue. This ultimately ensures that they can colonize the tissue and grow into metastases.

Specifically, the detached tumor cells release two inflammatory signaling molecules, known as interleukins, which stimulate fibroblasts in the lung to release two further inflammatory signaling molecules into the microenvironment: CXCL9 and CXCL10. In turn, these attach to a receptor molecule that several aggressive migrant cancer cells carry on their surface, marking a decisive step in the process of growing into a metastasis. These aggressive breast cancer cells thus benefit directly from the inflammation and from the signaling molecules CXCL9 and CXCL10.

"Interestingly, the very tumor cells that stimulate the fibroblasts to produce CXCL9 and CXCL10 also have the relevant receptor for these cytokines and thus benefit from the process," explained Maren Pein, lead author of the study. "That underlines how crucial the cellular communication between the detached cancer cells and the fibroblasts in their new microenvironment is for metastasis."

Furthermore, the scientists prevented metastasis in the lung in an experimental setting by treating mice with an inhibitor that blocked the receptor molecule on the cancer cells.

Tumor tissue samples from patients show that this cellular interaction probably plays a role in breast cancer patients too: Thus cancer cells that carry the relevant surface receptor and can therefore harness the interaction with fibroblasts to form metastases are also found in patients with metastatic breast cancer.

Oskarsson emphasized that it was still too early to identify a new treatment approach from these findings. "Our work is initially designed to help understand the underlying mechanisms that are necessary for metastases to actually arise," he explained. "But we obviously hope that this better understanding will lead to us being able to prevent metastases some time in the future."
-end-
*The Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH) is a partnership between DKFZ and the Dietmar Hopp Foundation

Maren Pein, Jacob Insua-Rodríguez, Tsunaki Hongu, Angela Riedel, Jasmin Meier, Lena Wiedmann, Kristin Decker, Marieke A.G. Essers, Hans-Peter Sinn, Saskia Spaich, Marc Sütterlin, Andreas Schneeweiss, Andreas Trumpp and Thordur Oskarsson: Metastasis-initiating cells induce and exploit a fibroblast niche to fuel malignant colonization of the lungs Nature Communications 2002, DOI: 10.1038/s41467-020-15188-x

A photo to accompany the press release is available for download at: https://www.dkfz.de/de/presse/pressemitteilungen/2020/bilder/Lungenmetastase.jpg


Photo caption: Lung metastasis in a breast cancer patient: the arrows indicate fibroblasts (brown) that communicate with metastatic cancer cells. Cell nuclei are stained blue.

Note on use of images related to press releases

Use is free of charge. The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) permits one-time use in the context of reporting about the topic covered in the press release. Images have to be cited as follows: "Source: Oskarsson, DKFZ/HI-STEM".

Distribution of images to third parties is not permitted unless prior consent has been obtained from DKFZ's Press Office (phone: ++49-(0)6221 42 2854, E-mail: presse@dkfz.de). Any commercial use is prohibited.

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. At DKFZ, more than 1,300 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful.

DKFZ's Cancer Information Service (KID) provides individual answers to all questions about cancer for patients, the general public, and health care professionals.

Jointly with partners from Heidelberg University Hospital, DKFZ runs the National Center for Tumor Diseases (NCT) located in Heidelberg and Dresden, and, also in Heidelberg, the Hopp Children's Cancer Center (KiTZ). In the German Cancer Consortium (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center at the NCT and DKTK sites is an important contribution to the endeavor of translating promising approaches from cancer research into the clinic in order to improve the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Related Cancer Cells Articles:

Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.
Engineered bone marrow cells slow growth of prostate and pancreatic cancer cells
In experiments with mice, researchers at the Johns Hopkins Kimmel Cancer Center say they have slowed the growth of transplanted human prostate and pancreatic cancer cells by introducing bone marrow cells with a specific gene deletion to induce a novel immune response.
First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable
Following the first US test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies -- for months.
Zika virus' key into brain cells ID'd, leveraged to block infection and kill cancer cells
Two different UC San Diego research teams identified the same molecule -- αvβ5 integrin -- as Zika virus' key to brain cell entry.
Plant-derived SVC112 hits cancer stem cells, leaves healthy cells alone
Study shows Colorado drug SVC112 stops production of proteins that cancer stem cells need to survive and grow.
Changes in the metabolism of normal cells promotes the metastasis of ovarian cancer cells
A systematic examination of the tumor and the tissue surrounding it -- particularly normal cells in that tissue, called fibroblasts -- has revealed a new treatment target that could potentially prevent the rapid dissemination and poor prognosis associated with high-grade serous carcinoma (HGSC), a tumor type that primarily originates in the fallopian tubes or ovaries and spreads throughout the abdominal cavity.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
White blood cells related to allergies may also be harnessed to destroy cancer cells
A new Tel Aviv University study finds that white blood cells which are responsible for chronic asthma and modern allergies may be used to eliminate malignant colon cancer cells.
Conversion of breast cancer cells into fat cells impedes the formation of metastases
An innovative combination therapy can force malignant breast cancer cells to turn into fat cells.
Breast cancer cells in mice tricked into turning into fat cells
As cancer cells respond to cues in their microenvironment, they can enter a highly plastic state in which they are susceptible to transdifferentiation into a different type of cell.
More Cancer Cells News and Cancer Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.