Researchers from the University of North Carolina Lineberger found that by helping to form clots in the tumors, immune cells that flock to a certain type of lung cancer, in fact form the basis for the spread of the tumor in the body.
In the journal Nature Communications, researchers report on a particular subset of tumor lung cancer, there is a high prevalence of immune cells known as inflammatory monocytes. These immune cells that normally help to improve wound healing, cancer also allow spreading to other parts of the body.
"The way in which these immune cells contribute to the metastasis of lung cancer, was very unexpected. They produce a large number of factors that leads to clots in the tumor in which tumor cells can penetrate to spread in the body, "- said UNC Laynerger Chad Peko, MD, Associate Professor of Medicine Hematology and Oncology, School of Medicine UNC and the corresponding author of the study. "Our goal - to use this information to teach cancerous wounds" heal itself ".
Previous studies have classified the light squamous cell carcinoma, which accounts for about 30 percent of all types of lung cancer, in four different types, based on their biological and molecular characteristics. In the new study Pekot and his team found that the light squamous cell carcinoma can be reclassified only in two different categories based on whether they showed a high presence of inflammatory monocytes.
They used the expression of CD14 gene as a biomarker to indicate that the high presence of immune cells is associated with poor survival.
"It is important to understand that while so much attention is paid to the activation of parts of the immune system to fight cancer in the majority of tumors is a process ambiguous" - Peko said. "There are immune cells that we want to activate, but there are other immune cells that we want to disable."
The researchers used a recently developed laboratory models of lung squamous cell carcinoma for studying the role of inflammatory monocytes. Tumors form CCL2 signal, which helps recruit inflammatory monocytes. These immune cells then release the coagulation factor XIIIA factor, which, according to Pekota creates a fibrin scaffold that rises across and then move to distant organs of the tumor cells.
"These findings shed new light on the functioning of the tumor microenvironment and could potentially lead to new approaches to targeting the metastasis of this extremely aggressive disease," - said Alessandro Porrello, Ph.D., a researcher at UNC Lineberger and the study's first author. Genetically modifying expression of CCL2 in metastasis model developed in their laboratories, they found that low expression is associated with decreased metastasis, whereas high expression is associated with enhanced metastatic features. They have demonstrated that the presence of the clot facilitates the movement and migration of cancer cells. In addition, the study of tumor samples from patients, they found that tumors with high cross-linking of fibrin associated with increased risk of tumor spread.
Researchers have been able to reduce metastasis using compound that blocks CCR2, the receptor on the surface of inflammatory monocytes. They observed a significant reduction of lung metastases. Peko said that they want to continue to study this strategy and possibly other ways to prevent coagulation in tumors, to make sure that the strategy prevents the onset of metastasis and learn whether it can stop the process after it begins.
"We want to make progress in patients with squamous cell carcinoma of the lungs and expand the therapeutic options available to these patients," - Peko said. "The more we understand the progression of the disease, including how metastases arise, the more we can understand how we can regress the disease, or just keep it under control."