Circulating Microvesicles from Pancreatic Cancer Accelerate the Migration and Proliferation of PANC-1 Cells.
Circulating Microvesicles from Pancreatic Cancer Accelerate the Migration and Proliferation of PANC-1 Cells.
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DOI：
10.1021/acs.jproteome.8b00014
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发表时间：
2018-04-06
影响因子：
4.4
通讯作者：
Lubman DM
中科院分区：
文献类型：
--
作者：
An M;Zhu J;Wu J;Cuneo KC;Lubman DM
循环微泡能够介导细胞间的远距离通讯。了解来自胰腺癌的微泡如何作用于体内其他细胞是至关重要的。在这项工作中，从10例局部晚期胰腺癌患者和健康对照中分离出血清来源的微泡。使用Cell Transwell和WST-1试剂，我们发现胰腺癌微泡加速了PANC-1细胞的迁移和增殖。同时，10 μM的吉西他滨对肿瘤微囊泡处理细胞（cmtc）的增殖影响小于健康微囊泡处理细胞（hmtc）。接下来，我们优化了过滤辅助制样方法，提高了蛋白质样品的回收率，并将其应用于CMTCs和HMTCs的蛋白质组定量。用液相色谱-串联质谱法对肽段进行标记和分析。总共鉴定出4102个蛋白，其中35个蛋白在CMTCs中上调，27个蛋白下调。我们通过Western blot验证了三个关键蛋白CD44、PPP2R1A和TP53的定量结果。独创性途径分析揭示了癌症微泡可能参与促进细胞迁移和增殖的途径。这些发现可能为肿瘤发生和转移的治疗提供新的线索。
Circulating microvesicles are able to mediate long-distance cell–cell communications. It is essential to understand how microvesicles from pancreatic cancer act on other cells in the body. In this work, serum-derived microvesicles were isolated from 10 patients with locally advanced pancreatic cancer and healthy controls. Using Cell Transwell and WST-1 reagents, we found that microvesicles from pancreatic cancer accelerated migration and proliferation of PANC-1 cells. Meanwhile, the proliferation of these cancer-microvesicle-treated cells (CMTCs) was affected less by 10 μM of gemcitabine relative to healthy microvesicle-treated cells (HMTCs). Next, we optimized the filter-aided sample preparation method to increase the recovery of protein samples and then applied it to the quantification of the proteome of CMTCs and HMTCs. The peptides were labeled and analyzed by liquid chromatography–tandem mass spectrometry. In total, 4102 proteins were identified, where 35 proteins were up-regulated with 27 down-regulated in CMTCs. We verified the quantitative results of three key proteins CD44, PPP2R1A, and TP53 by Western blot. The Ingenuity Pathway Analysis revealed pathways that cancer microvesicles might participate in to promote cell migration and proliferation. These findings may provide novel clues of treatment for tumorigenesis and metastasis.
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影响因子：
8.3
作者：
Coombes, Jason D.;Schevzov, Galina;Gunning, Peter W.
通讯作者：
Gunning, Peter W.
影响因子：
2.9
作者：
Kim J;Tan Z;Lubman DM
通讯作者：
Lubman DM
使用正电荷衍生化和串联 MS 谱图合并进行高置信度从头肽测序。
影响因子：
7.4
作者：
An, Mingrui;Zou, Xiao;Ji, Jianguo
通讯作者：
Ji, Jianguo
影响因子：
4.4
作者：
Han, Yan;Zhao, Jinghua;Wang, Daojing
通讯作者：
Wang, Daojing
影响因子：
4.6
作者：
Cappello, Francesco;Logozzi, Mariantonia;Fais, Stefano
通讯作者：
Fais, Stefano