Molecular and functional extracellular vesicle analysis using nanopatterned microchips monitors tumor progression and metastasis.
Molecular and functional extracellular vesicle analysis using nanopatterned microchips monitors tumor progression and metastasis.
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DOI：
10.1126/scitranslmed.aaz2878
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发表时间：
2020-06-10
影响因子：
17.1
通讯作者：
Zeng Y
中科院分区：
文献类型：
--
作者：
Zhang P;Wu X;Gardashova G;Yang Y;Zhang Y;Xu L;Zeng Y
纵向癌症监测对于精准医疗的临床实施至关重要。越来越多的证据表明细胞外囊泡（EV）在肿瘤的进展和转移中发挥重要作用，包括通过转运基质金属蛋白酶（MMPs）进行基质重塑。然而，EV的临床相关性在很大程度上仍未确定，部分原因是EV分析面临挑战。与现有技术主要集中在表征EV的分子成分不同，在这里，我们报告了一种纳米工程实验室芯片系统，该系统能够对肿瘤相关EV进行综合功能和分子表型分析。开发了一种通用的高分辨率胶体喷墨印刷方法，以允许三维（3D）纳米图案化器件的稳健和可扩展的制造。有了这个纳米芯片平台，我们展示了对EV上MMP 14的表达和蛋白水解活性的综合分析，以使用癌细胞系和小鼠模型检测体外细胞侵袭力并监测体内肿瘤转移。临床血浆标本的分析表明，我们的技术可用于癌症检测，包括在训练队列（n = 30，准确率96.7%）和独立验证队列（n = 70，准确率92.9%）中对年龄匹配的对照和导管原位癌、浸润性导管癌或局部转移性乳腺癌患者进行准确分类。通过临床验证，我们的技术可以提供一种有用的液体活检工具，以改善癌症诊断和患者肿瘤演变的实时监测，从而为个性化治疗提供信息。
Longitudinal cancer monitoring is crucial to clinical implementation of precision medicine. There is growing evidence indicating important functions of extracellular vesicles (EVs) in tumor progression and metastasis, including matrix remodeling via transporting matrix metalloproteases (MMPs). However, the clinical relevance of EVs remains largely undetermined, partially owing to challenges in EV analysis. Distinct from existing technologies mostly focused on characterizing molecular constituents of EVs, here we report a nanoengineered lab-on-a-chip system that enables integrative functional and molecular phenotyping of tumor-associated EVs. A generalized, high-resolution colloidal inkjet printing method was developed to allow robust and scalable manufacturing of three-dimensional (3D) nanopatterned devices. With this nanochip platform, we demonstrated integrative analysis of the expression and proteolytic activity of MMP14 on EVs to detect in vitro cell invasiveness and monitor in vivo tumor metastasis, using cancer cell lines and mouse models. Analysis of clinical plasma specimen showed that our technology could be used for cancer detection including accurate classification of age-matched controls and patients with ductal carcinoma in situ, invasive ductal carcinoma, or locally metastatic breast cancer in a training cohort (n = 30, 96.7% accuracy) and an independent validation cohort (n = 70, 92.9% accuracy). With clinical validation, our technology could provide a useful liquid biopsy tool to improve cancer diagnostics and real-time surveillance of tumor evolution in patients to inform personalized therapy.
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影响因子：
16.6
作者：
Clancy, James W.;Sedgwick, Alanna;Rosse, Carine;Muralidharan-Chari, Vandhana;Raposo, Graca;Method, Michael;Chavrier, Philippe;D'Souza-Schorey, Crislyn
通讯作者：
D'Souza-Schorey, Crislyn
影响因子：
4
作者：
Hakulinen, Juha;Sankkila, Lotta;Keski-Oja, Jorma
通讯作者：
Keski-Oja, Jorma
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D
影响因子：
64.5
作者：
Genschmer, Kristopher R.;Russell, Derek W.;Blalock, J. Edwin
通讯作者：
Blalock, J. Edwin
影响因子：
6
作者：
Doebar, Shusma C.;Sieuwerts, Anieta M.;van Deurzen, Carolien H. M.
通讯作者：
van Deurzen, Carolien H. M.