Researchers shed light on the role of extracellular vesicles in cancer progression

Researchers shed light on the role of extracellular vesicles in cancer progression

The advent of cell phones, the Internet, and various messaging platforms has enabled faster and broader communications around the world. But did you know that your body has its own complex communication system in the form of extracellular vesicles (EVs)? These small structures, containing cellular “cargo” such as proteins and nucleic acids, are secreted by cells and can travel throughout the body and influence a variety of physiological and pathological processes. Recently, researchers in Japan shed new light on the role of EVs in cancer progression.

In a new study published in Inflammation and Regeneration, researchers led by Tokyo Medical and Dental University (TMDU) examined the effects of oral cancer cell-derived EVs on endothelial-mesenchymal transition (EndoMT). EndoMT is a process in which endothelial cells, or cells lining blood vessels, lose their properties and take on properties of mesenchymal cells.

While EndoMT usually occurs during embryonic development, it has also been shown to destabilize vascular structures such as blood vessels. In cancer, vascular destabilization can make it easier for cancer cells to enter and exit the bloodstream, promoting metastasis. Previous research has shown that cancer cells release EVs that induce a similar process called epithelial-mesenchymal transition (EMT), thereby promoting tumor development. However, the effects of cancer cell EVs on EndoMT in normal vascular endothelial cells have not yet been elucidated. Therefore, the TMDU-led research team set out to characterize EVs released by oral cancer cells and examine the effects of these EVs on healthy vascular endothelial cells.

A signaling factor known as transforming growth factor-β (TGF-β) has been shown to induce EMT in cancer cells, so we began to examine characteristic changes in human oral cancer cells caused by TGF-β-induced EMT. We found that oral cancer cells exposed to TGF-β released approximately three times as many EVs as those that were not exposed.”

Miho Kobayashi, lead author

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Next, the research team incubated human vascular endothelial cells with EVs from cells exposed to TGF-β or EVs from cells not exposed to TGF-β. RNA and protein analyzes showed increased expression of mesenchymal cell markers and decreased expression of endothelial cell markers in vascular cells exposed to EVs secreted by cancer cells exposed to TGF-β.

“The changes in endothelial and mesenchymal marker expression in the vascular cells suggested that EndoMT was induced by EVs from oral cancer cells in which EMT had occurred,” says lead author Kashio Fujiwara. Furthermore, evaluation of the effects of cancer cell-derived EVs on vascular stability in human vascular endothelial monolayer cultures showed that EV treatment increased vascular destabilization.

This research provides further understanding of the mechanisms involved in EndoMT and vascular instability, which may aid in the development of therapeutic treatments to interrupt cancer progression and metastasis.

Source:

Tokyo University of Medicine and Dentistry

Reference:

Kobayashi, M., et al. (2022) Transforming growth factor-β-induced secretion of extracellular vesicles from oral cancer cells elicits endothelial barrier instability via the endothelial-mesenchymal transition. Inflammation and regeneration. doi.org/10.1186/s41232-022-00225-7.

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