Lung squamous carcinomas (LUSC) make up of 30% of all lung cancers and lung cancer as a whole is the leading cause of cancer-related deaths worldwide. The discovery of therapeutics for LUSC has been slow but a recent study has advanced the understanding of the disease which could lead to improved treatments. Researchers from University of North Carolina discovered that a certain type of LUSCs recruit inflammatory monocytes to the tumor which build a fibrin clotting scaffold that supports tumor growth and migration. Drugs that inhibit the signal which these immune cells follow to travel to the tumor may help prevent tumor metastases. The study findings were published in Nature Communications.
"The way that these immune cells promote lung cancer metastases was very unexpected. They produce a large amount of a factor that leads to clot in the tumor, which the tumor cells can latch onto and climb across to spread in the body," said UNC Lineberger's Chad Pecot, MD, assistant professor in the UNC School of Medicine Division of Hematology and Oncology and the study's corresponding author.
The researchers pointed out that there are certain types of immune cells that we want to activate in order to fight against cancer, however, there are other types that we want to turn off. The study used mouse models of LUSC to study the role of the ‘bad’ immune cells, inflammatory monocytes. It was discovered that the tumors produced a cytokine known as CCL2 to recruit the monocytes. The immune cells release Factor XIIIA, a clotting factor that creates a fibrin scaffold for the tumor to adhere to and travel to distant organs. The team demonstrated that the clot allowed the cancer cells to easily move and migrate.
Experiments also showed that high expression of CCL2 was linked to enhanced metastasis. When a compound blocked the CCL2 receptor on the surface of the inflammatory monocytes, the researchers observed a significant decrease in lung metastases. The team plans to continue to investigate other methods of inhibiting clotting within tumors to prevent metastases from occurring or stop the process once it has already begun.