In a new study published in the FASEB Journal by researchers at the University of Vermont, researchers show how exposure to asbestos can change the protein-levels in small fluid-filled sacs in a person’s lungs or bloodstream.

And, once these sacs meet up with mesothelial cells, it appears that these protein changes are what leads to mesothelial cells becoming cancerous.

Asbestos and Exosomes

The cells in humans’ bodies communicate with each other in many different ways. One way is through exosomes—a membranous vesicle or small fluid-filled sac, which travels outside of the cell’s walls.

In this study, the researchers theorized that when lung epithelial cells or macrophages (a type of white blood cell) came into contact with asbestos fibers, the cells release exosomes. These exosomes would then travel to the mesothelial cells to deliver their messages. Finally, the researcher thought once the information was received, it would cause the mesothelial cells to change and become cancerous.

The reason the researchers chose to focus on the epithelial cells from the lungs and the white blood cells is that these cells are the ones that tend to come into contact with asbestos first. While it is possible for the spear-like asbestos fibers to travel deeper within the lung, they usually stop in the upper respiratory tract that is the patient’s mouth, nose and throat from the vocal cords up.

Asbestos-Exposed Exosomes Change Mesothelial Cell Genes

Their research study showed that their theory was correct. When lung epithelial cells and macrophages came into contact with asbestos, they altered the protein-levels within the exosomes they released. These altered exosomes would then cause the mesothelial cells to change just as if the mesothelial cells came into direct contact with asbestos.

One of the proteins in the exosomes that increased after the asbestos-exposure was thrombospondin-1. This discovery is significant because this particular protein is often found in greater than normal amounts in mesothelioma tumors.

Past research has shown that when the body creates too much of specific proteins, those proteins can play a part in the development of tumors. So, this new study suggests that thrombospondin-1 might be one of the proteins that cause mesothelioma tumors to form.

Another protein that they found an over-representation of in the exosomes was glypican-1. The reason that discovery is important is this protein is already considered an exosomal indicator or biomarker of pancreatic cancer. Which means it is already known that the protein glypican-1 plays a part in causing other types of cancers.

What the Findings Mean for Mesothelioma Treatment

Right now there are no conclusive biomarkers that doctors can use to measure someone’s level of exposure to asbestos before they begin to develop mesothelioma. Meaning doctors can’t take a sample from a patient’s body and measure protein levels in mesothelial cells to determine if the cells are healthy or changing and likely to become cancerous.

But, with this new study, researchers are learning proteins might be biomarkers that could detect mesothelioma. As more research comes out, doctors will be able to determine the likelihood of asbestos exposure becoming cancer down the road. This can lead to discovering preventive methods exposed-exposed individuals can take to lower their chances of contracting mesothelioma.

This research may also lead to new treatments for mesothelioma. For example, other researchers are already looking at the effect of targeting the protein glypican-1 to treat different types of cancers. If it’s a biomarker for mesothelioma, those types of targeted therapies could be explored for mesothelioma.

As with all types of cancers, the sooner the tumors are detected, the more treatable they are. This new research means doctors are one step closer to being able to diagnose a patient with mesothelioma sooner, treat them earlier and treat them with more effective therapies.

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Sources
  1. BMC Biology. "Q&A: What are exosomes, exactly?" Retrieved from: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0268-z. Accessed April 9, 2018.
  2. NCBI. "Glypican-1 targeted antibody-based therapy induces preclinical antitumor activity against esophageal squamous cell carcinoma. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421884/. Accessed April 9, 2018.
  3. ResearchGate. "Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells." Retrieved from: https://www.researchgate.net/publication/323860708_Exosomes_from_asbestos-exposed_cells_modulate_gene_expression_in_mesothelial_cells. Accessed April 5, 2018.

Last modified: May 21, 2018