A new study shows proteins associated with extracellular vesicles might be used to detect cancer without the need for surgical biopsy. Extracellular vesicles (EVs) are lipid-enclosed particles that secrete proteins, lipids, and RNA from cells and play an important role in cancer progression. Because of their role in transferring biologically important molecules between cells, researchers are studying their role in cancer spread and as a promising source of circulating biomarkers.
In this study, researchers focused on palmitoylation, a process where enzymes load lipids onto proteins within EVs. Palmitoylation can affect where proteins are located within cells, their activities and their contribution to cancer progression. The process is frequently altered in various diseases, including cancer. But technical challenges—including low levels of palmitoyl protein, challenges in enriching them, and others— have thus stymied palmitoylation profiling and its further understanding its biological role within EVs.
To learn more about the palmitoylation signature within EVs, the investigators examined small and large EVs in samples of human prostate cancer cells. They developed a new technique that uses a metabolic labelling-independent, cysteine centric approach, known as low-background acyl-biotinyl exchange (LB-ABE), to identify specific palmitoyl-proteomic signatures in highly purified EVs isolated by density gradient. Because most abundant proteins are not palmitoylated, the LB-ABE may be useful for removing them from biofluids.
After sequestering the EVs via LB-ABE and centrifugation, the research team studied palmitoylation levels within the vesicles as well as the types of proteins within the vesicles and compared them with levels found in cells.
They found 97 palmitoyl-proteins were detected only in EVs, with 66 unique to L-EVs, 7 unique to S-EVs, and 24 common to both EV types. Further, EVs from the cancer cells contained palmitoylated proteins that are associated with the spread of cancer and 92 prostate cancer-specific/enriched genes. Specifically, they found STEAP1, STEAP2, and ABCC4 to be prostate cancer-specific palmitoylated proteins found in large quantities within both large and small EVs. When palymitoylation was chemically suppressed, the amounts of these proteins dropped.
This study suggests an important role of palmitoylation in the sorting of cargo to different EV populations that would be missed if only the native protein is investigated and could be useful for cancer detection via liquid biopsy.
“Our results suggest that protein palmitoylation may be involved in the selective packaging of proteins to different extracellular vesicle populations in the body,” said co-corresponding author of the study Dolores Di Vizio, MD, PhD, at Cedars-Sinai. “This finding raises the possibility that by examining these proteins in extracellular vesicles in the bloodstream, we may be able to detect and characterize cancer in a patient in the future without performing a surgical biopsy.”
.The team plans on further study with the goal of identifying clinically significant prostate cancer at diagnosis.