Malignant pleural mesothelioma includes three subtypes, but one is significantly more aggressive than the others and for a long time scientists could not figure why, until now. Researchers from the Comprehensive Cancer Center (CCC) of MedUni Vienna and Vienna General Hospital discovered an interaction that leads to this vigorous behavior.
The culprits are FGF2 and EGF, two growth factors that send signals which promote migration and therefore spread of cancer. In theory, blocking these signals could open the door for new approaches for treating this subtype of malignant pleural mesothelioma.
Many of the mechanisms that cause cancer are in fact processes that a healthy body generally requires in order to function normally. The issue arises when tumor cells take advantage of these processes to benefit their own development.
In wound healing, for example, it is crucial for cells that are anchored in one spot to be able to migrate. To allow this movement, a complex modification process is initiated within the cell, called epithelial-mesenchymal transition (EMT). This is what lets cells change their properties and their appearance. Cells that were once epithelial cells with high cell-cell adhesion and therefore immovable, transform into mesenchymal cells which can travel.
“EMT plays a key role in the development of metastases and in the local spread. Especially in the aggressive forms of malignant pleural mesothelioma, we could see that the tumour cells are very similar in appearance to mesenchymal cells”, noted molecular biologist Michael Grusch.
Along with his team, Grusch noticed that EMT was triggered by defined signals, namely so-called fibroblast growth factors (FGF2) and epidermal growth factors (EGF). They were bound to receptors on the surface of the tumor cells and forwarded the signal to modify into the cell interior.
To confirm their findings, researchers blocked the effect of FGF2 and EGF, observing an immediate loss of aggressiveness.
“Our results help to provide a better understanding of the disease. Blockading these signals could, therefore, offer new approaches for treating certain aggressive forms of mesothelioma”, added co-author Mir Ali Reza Hoda from the Department of Surgery at Vienna General Hospital.