The composition of the environment outside the cells where lung cancer is growing affects the ability of cancer cells to survive and spread to other areas of the body, including the brain, according to recent research.
Therefore, targeting the malignant components of this extracellular environment could be a promising approach to halt metastasis in lung cancer patients.
The findings were published in the scientific journal Cancer Research, a publication of the American Association for Cancer Research, in a report titled “Extracellular matrix receptor expression in subtypes of lung adenocarcinoma potentiates outgrowth of micrometastases.”
The study’s results have led to a collaboration with a pharmaceutical company to test drugs targeting that pathway, Dr. Don Nguyen, associate professor of pathology at Yale School of Medicine and senior author of the study, said in a press release.
The team analyzed RNA samples from lung cancer patients whose cancer had spread to the brain, and from patients without brain metastasis. They also used animal models of lung adenocarcinomas.
Lung cancer cells that had spread expressed a number of proteins that allowed them to survive outside the lungs in small numbers. These molecules were protecting the tumor cells from their environment.
“These occult lung cancer cells have found a unique way to co-opt the ‘brain microenvironment’ and survive,” Nguyen explained.
High levels of one particular extracellular molecule called hyaluronan-mediated motility receptor (HMMR), a molecular signature of inflammation, was associated with poor outcomes. The lungs and the brain are environments rich in hyaluronan, a scaffolding protein secreted by cells, which surrounds them. It binds to HMMR and mediates cell migration, explaining why the lung cancer cells spread particularly to the brain.
When the researchers lowered the level of HMMR, they saw that the ability of lung cells to form tumors and spread had diminished.
Lung cancer leads to the death of more people than the combination of breast, colon, and prostate cancers each year. Lung adenocarcinomas are a particularly lethal form of lung cancer, and can affect both smokers and non-smokers. One particular feature of this type of lung cancer is the spread of tumor cells to the brain. This study offers a novel molecular explanation as to how this may happen.