Glypican1 identifies cancer exosomes and facilitates early detection of cancer
By S. Melo, L. B. Luecke, Christoph Kahlert, A. Fernández, S. Gammon, Judith Kaye, Valerie S. LeBleu, E. Mittendorf, J. Weitz, N. Rahbari and 5 more. Nature, 2015
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Exosomes are lipid-bilayer-enclosed extracellular vesicles 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 the circulation is currently lacking. Using mass spectrometry analyses, we identify 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 patients and mice with cancer. GPC1+ crExos were detected in the serum of patients with pancreatic cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreatic disease from patients with early- and late-stage pancreatic cancer. Levels of GPC1+ crExos correlate with tumour burden and the survival of pre- and post-surgical patients. GPC1+ crExos from patients and from mice with spontaneous pancreatic tumours carry specific KRAS mutations, and reliably detect pancreatic intraepithelial lesions in mice despite negative signals by magnetic resonance imaging. GPC1+ crExos may serve as a potential non-invasive diagnostic and screening tool to detect early stages of pancreatic cancer to facilitate possible curative surgical therapy.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/d128676afbf97af415d6d6ee2eae497ddb34a6bf
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Citations in the corpus
- Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes (2016, background): “Consequently, the possibility of using these vesicles as biomarkers in various diseases, as vehicles of immunotherapies, or as targets to be eliminated to improve patients’ health is currently being explored (2, 6).”
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- Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis (2019, background): “There has also been success in finding markers for pancreatic cancer and lung cancer in exosomes as well [28,77].”
- Innovative approaches for cancer treatment: current perspectives and new challenges (2019, methodology): “GPC1-positive exosomes have been employed to detect pancreatic cancer [75], while circulating exosomal macrophage migration inhibitory factor (MIF) was able to predict liver metastasis onset [76].”
- Exosomes as a new frontier of cancer liquid biopsy (2022, background): “For example, anti-GPC-1 antibody and Alexa-488-tagged secondary antibody were introduced to the exosome-attached beads and the percentage of positive beads was therein referred as the percent of GPC-1+ exosomes [38].”
- Extracellular vesicles in cancer: cell-to-cell mediators of metastasis (2016, background): “Importantly, exosomal dsDNA reflects the oncogenic mutational status of the respective parental cancer cell (Kahlert et al., 2014; Melo et al., 2015; Thakur et al., 2014), highlighting the utility of exosomal dsDNA as valuable biomarker for the detection of oncogenic mutations in the clinical…”
- NONCODEV5: a comprehensive annotation database for long non-coding RNAs (2017, background): “…cancer, the researchers found that the abundance of GPC1 (glypican-1)-positive exosomes in the sera of patients with early pancreatic cancer was significantly higher than the abundance in the normal population; this finding provides a significant basis for the early diagnosis of cancer (52).”