Glypican-1 identifies cancer exosomes and detects early pancreatic cancer
Sonia A. Melo,Linda B. Luecke,Christoph Kahlert,Agustín F. Fernández,Seth T. Gammon,Judith Kaye,Valerie S. LeBleu,Elizabeth A. Mittendorf,Juergen Weitz,Nuh N. Rahbari,Christoph Reissfelder,Christian Pilarsky,Mario F. Fraga,David Piwnica-Worms,Raghu Kalluri +14 more
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TLDR
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.Abstract:
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.read more
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Oncogenic and Non-Malignant Pancreatic Exosome Cargo Reveal Distinct Expression of Oncogenic and Prognostic Factors Involved in Tumor Invasion and Metastasis.
TL;DR: Oncogenic exosomes contain factors known to regulate the pre‐metastatic niche, clinically‐relevant proteins which correlate with poor prognosis as well as protein networks involved in various cancer hallmarks including proliferation, invasion, metastasis, and immune surveillance escape.
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Proteomic and genomic profiling of pancreatic cancer
TL;DR: The integration of mass spectrometry and genomic sequencing strategies may help characterize protein identities and post-translational modifications that relate to a specific mutation in patients with pancreatic cancer.
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In Situ One-Step Fluorescence Labeling Strategy of Exosomes via Bioorthogonal Click Chemistry for Real-Time Exosome Tracking In Vitro and In Vivo.
S. H. Song,S. H. Song,Man Kyu Shim,Seungho Lim,Yujeong Moon,Yujeong Moon,Suah Yang,Suah Yang,Jinseong Kim,Jinseong Kim,Yeonsun Hong,Hong Yeol Yoon,In San Kim,In San Kim,Kwang Yeon Hwang,Kwangmeyung Kim,Kwangmeyung Kim +16 more
TL;DR: An in situ one-step bioorthogonal click chemistry offers improved labeling efficiency, biocompatibility and imaging sensitivy compared to standard exosomes (ST-Exo), purified with classical ultracentrifugation or carbocyanine lipophilic dye (DiD)-labeled exosome in vitro.
Journal ArticleDOI
Lipidomic characterization of extracellular vesicles in human serum.
Suming Chen,Amrita Datta-Chaudhuri,Pragney Deme,Alex M. Dickens,Raha Dastgheyb,Pavan Bhargava,Honghao Bi,Norman J. Haughey +7 more
TL;DR: New insights are provided into the lipid composition of EVs isolated from serum using a simple ultracentrifugation isolation method suitable for lipidomic analysis by mass spectrometry.
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Identification and Quantitation of Circulating Tumor Cells
TL;DR: This review aims to provide a comprehensive overview of CTC enrichment and detection techniques with an emphasis on novel approaches for rapid quantification of C TCs.
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