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本帖最后由 hzangs 于 2015-12-15 10:25 编辑
2015年6月24日《Nature》online一篇研究，题为<Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.> PMID 26106858
摘要：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.
大意：外泌体（exosome）是一种细胞分泌的脂质双层小体，内含蛋白及核酸，可以由细胞分泌后在血液循环中流动。目前尚无检测肿瘤来源的特异性exo的方法。本文研究者发现了一种蛋白多糖（glypican-1，GPC1），它可以富集于肿瘤细胞来源的exo。通过检测患者血清GPC1阳性的exo，可以区分健康人及胰腺癌患者。GPC1阳性的exo还可以作为患者术前、术后的预后指标。另外，分泌GPC1阳性的exo的患者及小鼠，携带特异性的KRAS突变，可以作为胰腺癌的早期诊断工具。
这篇paper最大的亮点在于发现GPC1在早期胰腺癌病人的血清exosome中丰度就显著高于正常人群，证明通过鉴定血清中分离的exosome中GPC1的丰度可以用来诊断早期胰腺癌，为治疗提供宝贵时间。文章思路清晰，样本数据充足可信。由于胰腺癌是目前最难诊断的癌症，很多胰腺癌病人都是到晚期才被诊断发现（例如，乔布斯--乔帮主），错过了治疗机会；这篇paper的发现为胰腺癌的前期诊断提供了十分重要的依据，为胰腺癌病人带来了福音，也可能会对胰腺癌的诊断带来颠覆性的改变。
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|Archiver|手机版|外泌体之家 | exosomes & microvesicles
发表于 2015-6-26 08:15:20
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