Researchers Discover New Mechanism Behind Spread of Mesothelioma
A team of researchers has discovered a mechanism that contributes to the behavior of one particularly aggressive subtype of malignant pleural mesothelioma (MPM).
MPM is divided into three subtypes: Epithelial, Sarcomatoid and Mixed, or Biphasic. Epithelial is the most common form of malignant pleural mesothelioma, and makes up about 60% of all cases. Sarcomatoid MPM comprises about 10% of all cases and these tumors display a more aggressive behavior. Biphasic contains elements of both Epithelial and Sarcomatoid MPM. This subtype accounts for the remainder of cases.
According to research team and Comprehensive Cancer Center (CCC) members, Michael Grusch and Karin Schelch (also lead author of the study), the tumor cells of the Sarcomatoid subtype “are able to assume special characteristics that promote migration and therefore spread of the cancer. This is possible because the cells receive the requisite signals for this spread from certain messenger substances, namely the two growth factors FGF2 and EGF.”
“By blockading these signals,” the researchers explained, “it might be possible to develop new approaches for treating this subtype of malignant pleural mesothelioma.”
Many mechanisms that cause cancer were originally processes that a healthy body needs to function normally. To promote tumor growth, tumor cells "exploit" many mechanisms, which were originally processes that a healthy body needs to function normally.
For example, the team wrote: “In some instances, such as embryonic development or wound healing, it is essential for cells that are anchored in one spot to be able to migrate. To allow this to happen, a complex modification process is initiated within the cell. This is known as epithelial-mesenchymal transition (EMT). As a result of EMT, the 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. These are cells with no fixed cell junctions that are therefore able to migrate and spread.”
Grusch explained: "EMT plays a key role in the development of metastases and in local spread. Especially in the aggressive forms of malignant pleural mesothelioma, we could see that the tumor cells are very similar in appearance to mesenchymal cells. In a petri dish, we have now investigated which biological signals cause the cancer cells to take on the characteristics of these mesenchymal cells."
The team found that, in aggressive MPM, “EMT is triggered by defined signals. These are, in fact, a group of so-called fibroblast growth factors (FGF2) and epidermal growth factors (EGF). These signaling substances bind to receptors on the surface of the tumor cells and forward the signal to modify into the cell interior.” Said Schelch: "If FGF2 and EGF are in play, the tumor subtype becomes more aggressive."
In an additional step, the research team showed that tumor cells “lost their aggressive characteristics again as soon as they encountered substances that blockade the effect of FGF2 and EGF.” According to Mir Ali Reza Hoda, CCC Department of Surgery and second lead author: "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.”
If you have been diagnosed with mesothelioma, a new or experimental treatment could be effective in helping treat the disease. Talk to your doctor about all of your options today.
Grusch, Michael, Karin Schelch, and Mir Ali Reza Hoda. “FGF2 and EGF induce epithelial-mesenchymal transition in malignant pleural mesothelioma cells via a MAPKinase/MMP1 signal.” National Center for Biotechnology Information (NCBI). U.S. National Library of Medicine (NLM), National Institutes of Health (NIH), 05 Apr. 2018. Web. 05 Feb. 2019.
“Malignant pleural mesothelioma: new mechanism of spread discovered.” Medical University of Vienna. Medical University of Vienna, 13 Dec. 2018. Web. 05 Feb. 2019.