Inflammatory signals from vesicles increase cancer cell aggressiveness and invasiveness

Pro-inflammatory M1 macrophages involved in immune responses accelerate the progression of melanoma through the extracellular vesicles they secrete, a recent study from the University of Eastern Finland shows. The findings were published in Cell Communication and Signaling.

 The study explored the molecular mechanisms by which extracellular vesicles secreted by pro-inflammatory M1 macrophages affect melanoma cells. Extracellular vesicles are small membrane-bound particles secreted by cells and used for intercellular communication. All cells secrete extracellular vesicles; however, they seem to play a particularly important role in intercellular communication in the tumor microenvironment.

Macrophages are white blood cells that migrate into the tumor microenvironment in many cancers. A high macrophage count has been shown to be associated with a poor prognosis, including in melanoma.

The new study demonstrated that extracellular vesicles secreted by M1 macrophages contain inflammatory mediators such as the cytokines TNFα and IL-1β, and that these signaling molecules are delivered into cancer cells via extracellular vesicles. The study also showed that extracellular vesicles secreted by M1 macrophages activate the NF-κB signaling pathway, which plays a central role in inflammation, in the target cells. The resulting inflammatory environment increases the aggressiveness and invasiveness of cancer cells, i.e., their ability to penetrate into surrounding tissue.

Tumor cells and macrophages in their microenvironment are in constant interaction with one another. Understanding these interaction mechanisms is essential for identifying new targets for cancer therapy.

We showed that extracellular vesicles secreted by M1 macrophages can enhance melanoma cell motility and, as a result, melanoma progression. They enhance inflammatory signals within the tumor microenvironment and create a favorable, self-sustaining inflammatory cycle for cancer cells to thrive in."

Kaisa Mäki-Mantila, Doctoral Researcher, University of Eastern Finland

The findings reveal a key mechanism by which macrophages and cancer cells communicate with one another. This opens up new avenues for discovering methods that could break the inflammatory cycle that fuels tumor growth.

The study was conducted in the Institute of Biomedicine at the University of Eastern Finland, in Associate Professor (Docent) Sanna Pasonen-Sepp?nen's group. The study was supported by iCANDoc, Cancer Foundation Finland, the North Savo Cancer Association, the Finnish Cultural Foundation, Paavo Koistinen Foundation, Orion Research Foundation and Kuopio University Foundation.