Glypican-1 identifies cancer exosomes and detects early pancreatic cancer

Abstract

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.

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

“…Another kind of nanoparticle is the liposome, which has the longest circulation time, when with a particle size between 80 and 150 nm, instead of being quickly eliminated by the liver or spleen 150. If EVs behave in the same way, the superior effect of Exos (or small EVs) for therapeutic use could be due to the peak of Exos particle size distribution being in the 80–150 nm range 28, 151. However, further study of EV subtypes is still needed.…”

Immunoaffinity‐based isolation of melanoma cell‐derived exosomes from plasma of patients with melanoma

“…Human tumours produce and release a variety of EV subtypes which originate from different cell compartments and differ in molecular and genetic composition, size and, potentially, in biological effects they mediate [18]. Among these various EV subtypes, exosomes, and especially TEX, have been the focus of intense scientific inquiry [19,20]. TEX have been reported to mediate immune suppression and to carry a variety of immunosuppressive molecules and factors known to interfere with immune cell functions [4,21].…”

Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017

“…EVs with glypican-1 on their surface were previously identified as a biomarker for pancreatic cancer [13]. Since this publication, several different laboratories have validated the concept that glypican-1 is enriched on the EVs derived from cancer cells [14].…”