Oncosomes May Be Keys to Cancer Detection

A section of a secondary tumor resulting from lung metastasis (left), stained with the protein cytokeratin 18, shows abundant large oncosome-like vesicles (right), as indicated by arrows.

Small vesicles in the bloodstream of prostate cancer patients have unique characteristics that may allow physicians in the future to detect the disease at an early stage and track its progression, according to a study led by a Cedars-Sinai researcher.

The vesicles, known as large oncosomes, can be released by tumor cells that have the ability to metastasize, or spread, prostate cancer to bones and other distant sites. Principal investigator Dolores Di Vizio, MD, PhD, hypothesized that quantitative analyses of proteins in these vesicles would make it possible to discriminate between prostate cancer patients and healthy individuals.

The multicenter study, recently published in the journal Oncotarget, indicated that one-third of the proteins in large oncosomes are specific to this type of vesicle and differ from other types of vesicles that can be released by tumor cells and benign cells. Researchers identified cytokeratin 18 (CK18) as a protein enriched in large oncosomes, and CK18-positive vesicles were identified in the blood of patients with prostate cancer.

"This is the first study demonstrating this research advance," said Di Vizio, a research scientist and associate professor of Surgery, Biomedical Sciences and Pathology. "Previous studies from our group had highlighted the correlation between the number of large oncosomes and tumor metastasis. But this is the first study that identifies specific markers for these particles and proves the existence of one of these markers in the blood of patients with prostate cancer."

The experiments also demonstrated that large oncosomes can induce alterations in the metabolism of cancer cells that are exposed to them. Taken together, according to Di Vizio, these observations indicate that large oncosomes represent a discrete vesicle type that may play a distinct role in tumor progression and be a source of cancer-specific markers.

Eventually, the study's findings could benefit patients by resulting in a clinical product for early detection of cancer or monitoring the disease, Di Vizio said. "We are currently working on ways to facilitate the adaptation of our discovery to clinical laboratory tests that can be used routinely in patients with prostate cancer and possibly other tumor types," she added.

The research, performed at Cedars-Sinai between 2012 and 2014, benefited from collaboration with Michael Freeman, PhD, vice chair of Research and Surgery in the Department of Surgery, director of Cancer Biology and Therapeutics in the Department of Biomedical Sciences and professor of Surgery and Biomedical Sciences; and Wei Yang, PhD, director of the Biomarker Discovery Platform Core for large-scale, quantitative mass spectrometry and assistant professor of Surgery. The team used cell cultures and procedures to isolate large oncosomes previously developed in the Di Vizio laboratory. Most of the study was conducted in vitro, but the results also were confirmed in the blood of human subjects.

Human samples were obtained from collaborators Martin Gleave, MD, and Emma Tomlinson Guns, PhD, both of the University of British Columbia in Vancouver. Other collaborators on the study included researchers from the Pohang University of Science and Technology in Pohang, South Korea, and La Trobe University in Bundoora, Australia.