Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.
Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.
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DOI：
10.1038/nature14581
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发表时间：
2015-07-09
期刊：
影响因子：
64.8
通讯作者：
Kalluri R
中科院分区：
文献类型：
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作者：
Melo SA;Luecke LB;Kahlert C;Fernandez AF;Gammon ST;Kaye J;LeBleu VS;Mittendorf EA;Weitz J;Rahbari N;Reissfelder C;Pilarsky C;Fraga MF;Piwnica-Worms D;Kalluri R
外泌体是脂质双层封闭的细胞外囊泡（EVs），含有蛋白质和核酸。它们由所有细胞分泌并在血液中循环。目前缺乏循环中癌细胞衍生外泌体的特异性检测和分离。通过质谱分析，我们鉴定出了一种细胞表面蛋白聚糖，glyican -1 (GPC1)，专门富集于癌细胞来源的外泌体上。采用流式细胞术从癌症患者和癌症小鼠血清中监测和分离GPC1+循环外泌体（crExos）。在胰腺癌患者血清中检测GPC1+ crExos具有绝对的特异性和敏感性，可将健康人、胰腺良性病变患者与早、晚期胰腺癌患者区分开来。GPC1+ crExos水平与肿瘤切除前后患者的肿瘤负荷和生存相关。由致癌性KRAS驱动的自发性胰腺肿瘤患者和小鼠的GPC1+ crExos含有特异性KRAS突变的RNA，尽管小鼠MRI信号为阴性，但GPC1+ crExos是检测PanIN病变的可靠生物标志物。GPC1+ crExos可能作为一种潜在的无创诊断和筛查工具，用于发现早期胰腺癌，促进可能的根治性手术治疗。
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.