Researchers from Vienna, Austria recently uncovered one of the reasons sarcomatoid mesothelioma can spread so quickly—it changes the shape of its cells so they are more adept at traveling around the body. Fortunately, the researchers also uncovered how sarcomatoid cells make these changes, and they’ve potentially come up with a way to stop it.

Why Sarcomatoid Cells Spread so Quickly

All human bodies have an ability called epithelial-mesenchymal transition (EMT). This is when the body takes a cell that is usually stationary and changes the way it looks and acts so that it can be used in a different part of the body. Typically, this happens under particular conditions, such as when an embryo is growing into a baby or when an individual has a cut that heals.

However, sarcomatoid mesothelioma—one of three primary mesothelioma cell types—can hijack this natural process and cause it to make those same changes to cancerous cells.

According to the study by researchers from the Comprehensive Cancer Center (CCC) of MedUni Vienna and Vienna General Hospital, sarcomatoid cells change their shape from a box to a slender football. This shape change, combined with the messages the cells receive to move elsewhere in the body, causes sarcomatoid mesothelioma’s aggressive spread (metastasis).

Michael Grusch, one of the principal investigators, explained the reason they decided to explore the connection between EMT and sarcomatoid mesothelioma: “We could see that the tumor cells are very similar in appearance to mesenchymal cells.” In other words, they could see the sarcomatoid cells looked similar to ones that undergo the healthy EMT process.

Now, because of Grusch and Karin Schelch, the other lead investigator, scientists know which biological signals cause sarcomatoid cells to take the appearance and habits of mesenchymal cells. Those biological signals are two messenger growth factors (substances that stimulate growth)—fibroblast growth factors (FGF2) and epidermal growth factors (EGF).

As Schelch points out: “If FGF2 and EGF are in play, the tumor subtype becomes more aggressive.” These messenger growth factors carry messages that tell the cancerous cells what they require to change their appearance. The growth factors then transfer this message to the cancerous cells by attaching themselves to specific locations on the cell’s outer wall.

Developing Future Sarcomatoid Mesothelioma Treatments

While this discovery shows scientists how sarcomatoid mesothelioma gets help to spread faster, it also shows researchers what is happening so they can work to stop the process. The study by Grusch and Schelch is probably going to be the beginning of a chain of different studies that are all working towards stopping FGF2 and EGF from spreading their messages.

Grusch and Schelch helped with that too. Once they discovered that it’s the FGF2 and EGF signals causing the cancerous cells to become more mobile, they began looking for ways to block the signals. During testing done in a Petri dish, they successfully prevented the messages from being sent to other cells.

As soon as the FGF2 and EGF growth signals were blocked, the sarcomatoid cells became unaggressive.

Because their research was conducted in Petri dishes (and not in humans), it will be a while until their research translates into readily available treatments for patients with sarcomatoid cell type. If pre-clinical trials go well and the medication used to block FGF2 and EGF appears safe for humans, the medicine will move into clinical trials to be made available to patients.

In the clinical trials, researchers will look at how the drug reacts inside human bodies, how much of it is needed to be effective, whether that dosage is safe for humans, what the side effects are, and whether or not it stops the cancer from spreading.

Hopefully, this research will turn into medicine or another form of treatment that instantly stops the message from FGF2 and EGF, so that the sarcomatoid mesothelioma cells are no longer able to transform and spread aggressively throughout the body, making it easier to treat.

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Sources
  1. "New transmission route discovered for malignant pleural mesothelioma" Medical X Press. Retrieved from: https://medicalxpress.com/news/2018-12-transmission-route-malignant-pleural-mesothelioma.html. Accessed January 14, 2019.
  2. "FGF2 and EGF induce epithelial-mesenchymal transition in malignant pleural mesothelioma cells via a MAPKinase/MMP1 signal" NCBI. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/29635378. Accessed January 14, 2019.

Last modified: January 29, 2019