Summary
Exosomes are lipid bilayer-enclosed extracellular vesicles (EVs) that
contain proteins and nucleic acids. They are secreted by all cells and circulate
in the blood. Specific detection and isolation of cancer cell-derived exosomes
in circulation is currently lacking. Using mass spectrometry analyses, we
identified a cell surface proteoglycan, glypican-1 (GPC1), specifically enriched
on cancer cell-derived exosomes. GPC1+ circulating exosomes
(crExos) were monitored and isolated using flow cytometry from the serum of
cancer patients and mice with cancer. GPC1+ crExos were
detected in the serum of patients with pancreas cancer with absolute specificity
and sensitivity, distinguishing healthy subjects and patients with a benign
pancreas disease from patients with early and late stage pancreas cancer. Levels
of GPC1+ crExos correlate with tumor burden and survival in
patients pre- and post-surgical tumor resection. GPC1+ crExos
from patients and from mice with spontaneous pancreas tumors driven by oncogenic
KRAS contained RNA with specific KRAS mutation, and it emerges as a reliable
biomarker for the detection of PanIN lesions despite negative signal by MRI in
mice. GPC1+ crExos may serve as a potential non-invasive
diagnostic and screening tool to detect early stages of pancreas cancer to
facilitate possible curative surgical therapy.