Water in the chest – new findings on pleural effusion

February 28, 2018, Helmholtz Association of German Research Centres
Water in the chest – new findings on pleural effusion
The analysis shows a specific reaction of KRAS mutant cells to the messenger IL-1b in red. Other messengers had no effect (blue). Credit: Helmholtz Zentrum München

Lung cancer patients are particularly susceptible to malignant pleural effusion, when fluid collects in the space between the lungs and the chest wall. Researchers at the Helmholtz Zentrum München, in partnership with the German Center for Lung Research (DZL), have discovered a novel mechanism that causes this to happen. Their study, published in Nature Communications, now refines the mechanistic picture.

Malignant pulmonary effusion (MPE) frequently occurs in patients with metastatic breast or lung cancer. It involves a build-up of excess fluid in the pleural cavity, the area between the lungs and the , with accompanying malignant cells. The lung is surrounded by fluid, which can cause shortness of breath and chest pain, for example, and may even prove fatal.

"The cause is still not fully understood, which makes the search for suitable therapies more difficult," explains Professor Georgios Stathopoulos, research group leader at the Institute of Lung Biology (ILBD) and the Comprehensive Pneumology Center (CPC) at Helmholtz Zentrum München. "However, we've now made significant progress in that direction."

In their recent work, the team built on findings which they had also published in Nature Communications in May 2017. "At the time, we were able to show that pleural effusion is triggered by cancer cells with a malignant mutation in the KRAS gene," says Dr. Antonia Marazioti, lead author of the paper and scientist at the Molecular Respiratory Carcinogenesis Research Group in the medical department of the University of Patras, which is also led by Georgios Stathopoulos in close connection to his ILBD/CPC work at the Helmholtz Zentrum München.

Credit: Helmholtz Zentrum München

The authors have now been able to expand on this knowledge. "Our experiments show that inflammatory messengers of the immune system − notably interleukin-1β − activate a signaling pathway in mutated cancer cells, which in the long term can lead to pleural effusion," Stathopoulos explains. The molecule IKKα plays a key role in the signaling pathway in that it, in turn, releases other messengers (CXCL1), resulting in a strong inflammatory response (see illustration). "Consequently, those cells migrate to the via the spleen, where they cause effusion," explains the lung expert.

Double-pronged inhibition is better

To determine whether the findings might prove relevant to future treatment strategies, the researchers suppressed the newly discovered signaling pathway in the experimental model from two sides. In their double-pronged approach, they used both an inhibitor of KRAS and an inhibitor of IKKα. "In fact, this dual strategy significantly reduced both the incidence and the progression of MPE," Stathopoulos reports. Resistance to a single treatment was also reduced.

"Nearly two thirds of all MPEs are the result of . Given the large number of people who still smoke, appropriate therapies are urgently needed," Georgios Stathopoulos says. "Our findings suggest that drugs could become a therapeutic option for suppressing the mechanism we've discovered. We plan to investigate this line of enquiry in greater depth in the future and to further confirm the results in the translational approach with in collaboration with the Asklepiosklinik in Gauting."

Explore further: How cancer cells flood the lung

More information: Antonia Marazioti et al. Myeloid-derived interleukin-1β drives oncogenic KRAS-NF-κΒ addiction in malignant pleural effusion, Nature Communications (2018). DOI: 10.1038/s41467-018-03051-z

Related Stories

How cancer cells flood the lung

May 19, 2017
Lung cancer patients are particularly susceptible to malignant pleural effusion, when fluid collects in the space between the lungs and the chest wall. Researchers at the Helmholtz Zentrum München, in partnership with the ...

Unique lipid profile could help diagnose and treat lung cancer

September 8, 2017
The lipid contents of a fluid that surrounds the lungs in some diseases contains specific fats that could be used as a biomarker to distinguish people with and without lung cancer. It can also identify a subtype of the cancer ...

Study examines treatments for relieving breathing difficulties among patients with lung effusions

May 20, 2012
Helen E. Davies, M.D., of the University Hospital of Wales, Cardiff, and colleagues compared the effectiveness of treatments to relieve breathing difficulties among patients with malignant pleural effusion (presence of fluid ...

Lymph node stage may have clinical significance among NSCLC patients with stage IV M1a

August 24, 2016
Analysis of a large non-small cell lung cancer (NSCLC) patient cohort with stage IV M1a disease identified lymph node staging as having clinical significance and an impact on prognosis.

Effectiveness of pain medications for patients receiving treatment for lung condition

December 22, 2015
Use of NSAIDs vs opiates resulted in no significant difference in measures of pain but was associated with more rescue medication (additional medicine needed due to uncontrolled pain) among patients with malignant pleural ...

How the lungs of premature babies can undergo damage

September 29, 2017
Premature babies that need ventilation to support their breathing often suffer from a condition known as bronchopulmonary dysplasia. Researchers at the Helmholtz Zentrum München, partner in the German Center for Lung Research ...

Recommended for you

Scientists discover chemical which can kill glioblastoma cells

August 15, 2018
Aggressive brain tumour cells taken from patients self-destructed after being exposed to a chemical in laboratory tests, researchers have shown.

Three scientists share $500,000 prize for work on cancer therapy

August 15, 2018
Tumors once considered untreatable have disappeared and people previously given months to live are surviving for decades thanks to new therapies emerging from the work of three scientists chosen to receive a $500,000 medical ...

PARP inhibitor improves progression-free survival in patients with advanced breast cancers

August 15, 2018
In a randomized, Phase III trial led by researchers at The University of Texas MD Anderson Cancer Center, the PARP inhibitor talazoparib extended progression-free survival (PFS) and improved quality-of-life measures over ...

New clues into how 'trash bag of the cell' traps and seals off waste

August 15, 2018
The mechanics behind how an important process within the cell traps material before recycling it has puzzled scientists for years. But Penn State researchers have gained new insight into how this process seals off waste, ...

RUNX proteins act as regulators in DNA repair, study finds

August 15, 2018
A study by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has revealed that RUNX proteins are integral to efficient DNA repair via the Fanconi Anemia (FA) ...

Chemicals found in vegetables prevent colon cancer in mice

August 14, 2018
Chemicals produced by vegetables such as kale, cabbage and broccoli could help to maintain a healthy gut and prevent colon cancer, a new study from the Francis Crick Institute shows.

0 comments

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.