Cellular communication is vital for passing information to neighboring cells. One key messenger in this process is an exosome, a nanosized particle that buds off from a progenitor cell, carrying molecular cargo. Because these small, cellular vehicles carry contents from their parent cells, exosomes can serve as snapshots for a given population of cells, including tumors.
“If you can sample a vesicle, or any entity, from blood, it gives you a huge advantage, being a low or minimally invasive strategy to monitor cancer or detect cancer,” said David Greening, a biologist who studies extracellular vesicles like exosomes at La Trobe University.
One strategy to improve the use of exosomes as cancer biomarkers is to identify surface proteins on these vesicles that reflect their originating tumor. L-type amino acid transporter 1 (LAT1), a surface protein that shuttles large amino acids into the cell, is predominantly associated with cancerous cells and correlates with tumor severity. These characteristics made the protein an attractive target for therapeutic intervention, with one LAT1 inhibitor currently undergoing clinical trials.
In a study published in Scientific Reports, researchers demonstrated the potential of LAT1 on exosomes from pancreatic and other cancer cell lines as a biomarker. “[Now] we can detect and treat cancer using the same target,” said Ryuichi Ohgaki, a pharmacologist at Osaka University and study coauthor.
Ohgaki and his team studied the role of LAT1 in driving cancer progression for years. Inspired by previous work that measured cancer-associated proteins on exosomes, the group set out to investigate the correlation between LAT1 expression on exosomes and their originating cancer cells.
To explore this relationship, the team used ultracentrifugation to isolate these particles from human pancreatic, cervical, and bile duct tumor cell lines. In most of the tested cell lines, LAT1 expression on exosomes correlated with LAT1 expression on cell membranes.
To study exosomes in vivo, the team introduced pancreatic cancer cells into the peritoneal cavity of mice. One month later, they used immunohistochemistry to measure LAT1 expression in tumor tissue and adjacent nontumor cells, finding the protein exclusively in the tumor tissue. When they isolated exosomes from the peritoneal cavities of tumor-bearing and control mice, they detected greater LAT1 expression on the vesicles from the mice with tumors.
By Shelby Bradford, PhD
Article can be accessed on: The Scientist