Probe the molecular mechanisms of metastases

Cells have a sort of diffusion system. They can free tiny molecular balls, called extracellular vesicles (electric vehicles), which contain biological materials or messages and attach to other cells to share everything they contain.

In cancer, electric vehicles often deviate from tumor cells to sow cancer elsewhere in the body, leading to metastases. However, how electric vehicles connected to beneficiary cells to deliver their payload have remained a mystery – until now. A team of researchers based in Japan has revealed the molecular mechanisms underlying the process for small electric vehicles (SEV), which, they say, could have implications to develop better treatment against cancer.

The team published their conclusions in the Journal of Cell Biology.

“In recent years, electric vehicles have drawn significant attention as mediators of intercellular communication,” said corresponding author Kenichi Gn Suzuki, professor at the Glyco-Core research institute at GIFU University in Gifu and head of the Advanced Bioimaging, National Cancer Research Institute in Japan.

He explained that electric vehicles can serve as biomarkers because they transport specific proteins and genetic materials that may indicate the progression of the disease. Researchers also started exploring their potential to treat cancer, either by inhibiting their liaison to host cells, or by encouraging the link of electric vehicles with useful therapeutic loads.

“However, the mechanisms underlying their selective connection to receiving cell membranes have remained elusive,” said Suzuki. “In this study, we sought to elucidate these mechanisms.”

Researchers focused on understanding the role of integrine heterodimers, which are molecules that help SEVS join the host cell. The team previously noted that SEVs could be sorted in subtypes with different properties, according to the Tetraspanine protein. This type of protein is small but essential for the training and regulation of the EV, said Suzuki.

Using this understanding, researchers sorted and followed the SEV with a single molecule resolution.

They examined the sorted subtypes with super-resolution microscopy to note that all subtypes mainly used integrine heterodimers associated with a specific tetraspanin protein known as CD151 and a molecule containing carbohydrates and fats called GM1 to bind to the lamin, a critical protein with cellular membranes and Involved in the structure of the cell membrane and cell adhesion and cellular adhesion.

Laminine is specifically glycoprotein, which means that it is a protein with a molecule of carbohydrates or sugar attached to it. It exists in the extracellular matrix or in the molecular network surrounding the cells and supports their signage and their structure.

“Quantitative analysis using single-molecule imaging and super-resolution microscopy demonstrated that all EV subtypes derived from Four distinct tumor cell lines, irrespective of size, predominantly bind to laminin via cd151-associated integrin heterodimers and gm1, thereby eliciting Cells, “Suzuki Said, Noting that Evs Bound to Laminin significantly More than Bound to fibronectin, which is another protein responsible for cell membership in the extracellular matrix.

He also pointed out that two other proteins associated with membership in electric vehicles, Talin and Kindlin, have not activated the heterodimers of the integrine. Taken together, the researchers concluded that GM1 and the integrine heterodimers associated with the CD151 are essential for the EV link. This understanding, said Suzuki, could help researchers better inhibit or encourage binding to the need for the treatment of the disease.

“While electric vehicles have been widely explored as biomarkers, attempts to use electric vehicles as therapeutic agents have started,” said Suzuki. “Given our elucidation of molecular mechanisms underlying the binding of EVs to receiving cells, our results should advance the development of therapy based on electric vehicles.”