How cancer cells flood the lung

May 19, 2017
Cells isolated from a malignant pleural effusion. Mutation of KRAS was identified in the tumor cell clone (bottom right). 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, also shows that various active substances could potentially be used to treat this condition.

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

"There is still no effective treatment for this," explains Professor Georgios Stathopoulos, research group leader at the Institute for Lung Biology (ILBD) and Comprehensive Pneumology Center (CPC) at the Helmholtz Zentrum München. "In the case of larger pulmonary effusions with volumes exceeding one liter, treatment usually involves aspiration in order to relieve pressure on the lung."

Cancer cells trigger mechanism

Stathopoulos and his team are working to understand the causes of pleural effusion, which remain unclear, in an effort to advance the treatment of this condition in the future. In the current study, the scientists examined cancer cells they had obtained from pleural effusions with a malignant mutation in the KRAS gene. KRAS is known to play a key role in the growth of various malignant tumors.

"We were able to show that these cells release a messenger substance into the bloodstream, which in turn attracts immune cells. These cells then wander via the spleen to the pleural cavity, where they cause the effusion," Stathopoulos says, explaining the mechanism. In addition, the scientists found the KRAS-mutant cancer cells in the MPE material of as well as in the cell lines derived from them.

Tests on active substances to treat pleural effusion

In order to verify whether their newly acquired knowledge could be applied in clinical practice, the researchers tested two active substances that interrupt the mechanism at two different points. In an experimental model they were able to demonstrate that both the KRAS inhibitor Deltarasin and an antibody against the messenger substance released by the prevented pleural effusion.

"Nearly two thirds of all MPEs are the result of . In view of the still large numbers of smokers, appropriate treatments are urgently needed," Stathopoulos stresses. "Our results lead us to assume that drugs that target the mechanism we have discovered could be a potential treatment option. Further studies are now needed to confirm that."

Lung cancer expert Georgios Stathopoulos joined the Helmholtz Zentrum München in 2015. He also heads a working group at the Laboratory for Molecular Respiratory Carcinogenesis at the University of Patras in Greece. The study that has now been published was the outcome of collaboration between the two working groups.

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

More information: Theodora Αgalioti et al. Mutant KRAS promotes malignant pleural effusion formation, Nature Communications (2017). DOI: 10.1038/ncomms15205

Related Stories

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 ...

Study of potential new treatment for mesothelioma open to patients

September 15, 2016
The Baylor College of Medicine Mesothelioma Treatment Center at Baylor St. Luke's Medical Center has begun enrolling patients in a clinical research study looking at an investigational drug in patients with malignant pleural ...

Active agent from the Caribbean sea cucumber could improve treatment for malignant pleural mesothelioma

October 24, 2016
Researchers at the Comprehensive Cancer Center of MedUni Vienna and Vienna General Hospital have discovered a new option for treating malignant pleural mesothelioma. For the first time in the world, they were able to show ...

Ros1 gene fusions found in 2.4% of Asian patients with lung adenocarcinoma, associated with young age at diagnosis

July 21, 2014
ROS1 fusion genes were successfully detected independent of gender or smoking history in young East Asian patients with lung adenocarcinoma, a histological subgroup in non-small cell lung cancer (NSCLC), using multiplex reverse ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

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.