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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Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating Extracellular Vesicles.
Anbarasu Kannan,Julie V. Philley,Kate L. Hertweck,Harrison Ndetan,Karan P. Singh,Subramaniam Sivakumar,Robert B. Wells,Ratna K. Vadlamudi,Santanu Dasgupta +8 more
TL;DR: SPANXB1 represents a novel and ideal therapeutic target for blocking TNBC metastases due to its unique expression pattern and may function as an EV based prognostic marker to improve TNBC survival.
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Mass spectrometry-based proteomics revealed Glypican-1 as a novel ADAM17 substrate.
Rebeca Kawahara,Daniela C. Granato,Sami Yokoo,Romênia R. Domingues,Daniel M. Trindade,Adriana Franco Paes Leme +5 more
TL;DR: GPC1 is a novel ADAM17 substrate, thus the function of GPC1 may be modulated by proteolysis signaling, and Glypican-1 was validated as a novel substrate forADAM17, with important function in adhesion, proliferation and migration of carcinoma cells.
Journal ArticleDOI
Molecular detection of pancreatic neoplasia: Current status and future promise.
TL;DR: The current status of molecular markers for detection of pancreatic cancer in blood, Pancreatic cyst fluid, pancreatic juice and stool is discussed and some promising preliminary results of new approaches that have the potential of advancing this field in the near future are highlighted.
Journal ArticleDOI
Developments in miRNA gene signaling pathways in pancreatic cancer
TL;DR: The current review focuses on latest advances with respect to the roles of miRNAs in pancreatic ductal adenocarcinoma associated signaling pathways and miRNA-based therapeutics.
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Single-EV analysis (sEVA) of mutated proteins allows detection of stage 1 pancreatic cancer
Scott W. Ferguson,Katherine S. Yang,Piotr Zelga,Andrew S. Liss,Jonathan C. T. Carlson,Carlos Fernandez-del Castillo,Ralph Weissleder +6 more
TL;DR: The potential for sEVA for early cancer detection is established in a blinded study involving 16 patients with surgically proven stage 1 PDAC, and KRASmut and P53mut protein was detectable at much lower levels, generally in <0.1% of vesicles.
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