Exosomal proteins lay the foundation for cancer biomarkers

CCellular communication is critical for relaying messages to neighboring cells. A key messenger in this process is exosomes, nanoparticles that sprout from progenitor cells and carry molecular cargo. Because these small cellular carriers carry contents from their parent cells, exosomes can serve as snapshots of specific cell populations, including tumors.

“If you could collect vesicles or any physical sample from the blood, it would give you a huge advantage in terms of monitoring cancer or detecting Low-invasive or minimally invasive strategies for cancer.

One strategy to improve the use of exosomes as cancer biomarkers is to identify surface proteins on these vesicles that reflect their tumor of origin.¹ L-type amino acid transporter 1 (LAT1), a surface protein that transports large amino acids into cells, is primarily associated with cancer cells and correlates with tumor severity.^2,3 These properties make the protein an attractive target for therapeutic intervention, and one LAT1 inhibitor is currently in clinical trials.⁴

In a study published in scientific reportThe researchers demonstrated the potential of LAT1 on exosomes from pancreatic and other cancer cell lines as a biomarker. ⁵ “[Now] We can use the same target to detect and treat cancer,” said Ryuichi Ohgaki, a pharmacologist at Osaka University and study co-author.

Ohgaki and his team have studied LAT1’s role in driving cancer progression for years. Inspired by previous work measuring cancer-related proteins on exosomes, the team set out to study the correlation between LAT1 expression on exosomes and the cancer cells from which they originated.

To explore this relationship, the team used ultracentrifugation to isolate these particles from human pancreatic, cervical and bile duct tumor cell lines. In most cell lines tested, LAT1 expression on exosomes correlated with LAT1 expression on the cell membrane.

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 the tumor tissue and adjacent non-tumor cells and found that the protein was only present in the tumor tissue. When they isolated exosomes from the peritoneal cavities of tumor-bearing and control mice, they found higher expression of LAT1 on the vesicles of the tumor-bearing mice.

Ohgaki said the advantage of using LAT1 as a biomarker lies in its dual potential as a diagnostic and therapeutic target. To achieve this goal, he and his team are exploring ways to optimize the use of LAT1 in exosomes. One approach involves developing an antibody that detects the surface-exposed portion of LAT1. Although LAT1 is a surface marker, the team used an antibody that recognized the intra-exosome region of the protein, which required them to lyse exosomes to confirm LAT1 expression.

“If we could make such an antibody, we could directly detect LAT1 through a liquid biopsy such as blood or plasma,” Ohgaki said. Greening, who was not involved in the study, also highlighted the use of antibodies to target the surface portion of LAT1. to enhance its potential as a biomarker.

Furthermore, establishing more sensitive methods to identify LAT1 on exosomes could also improve its detection of lower volume exosomes, such as in the blood and in early stages of cancer progression. Greening said that because in vitro studies compared exosomes from cancer cells, he was also interested in understanding LAT1’s ability to differentiate between exosomes from healthy cells and diseased cells.

“These are fairly preliminary findings in terms of whether we can identify markers in extracellular vesicles that might indicate the onset of pancreatic cancer,” Greening said. However, because pancreatic cancer has limited diagnostic and treatment options, he added , there is a need to identify early markers of the disease. “There’s huge potential here to find something that could help many patients.”