Characterisation of tumour-derived microvesicles in cancer patients' blood and correlation with clinical outcome.
Characterisation of tumour-derived microvesicles in cancer patients' blood and correlation with clinical outcome.
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DOI：
10.1080/20013078.2017.1340745
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发表时间：
2017
影响因子：
16
通讯作者：
Binder C
中科院分区：
文献类型：
--
作者：
Menck K;Bleckmann A;Wachter A;Hennies B;Ries L;Schulz M;Balkenhol M;Pukrop T;Schatlo B;Rost U;Wenzel D;Klemm F;Binder C
为了评价来源于细胞膜的肿瘤微囊泡(T-MV)是否是合适的肿瘤生物标志物，我们从局部晚期和/或转移性实体瘤癌症患者(n=303，其中头颈癌79例，肺癌74例，乳腺癌41例，结直肠癌28例，其他类型癌症108例)和对照组(n=103n)的外周血中分离出微囊泡。用流式细胞术对整个MV制剂进行表征。携带肿瘤相关蛋白MUC1、EGFR和EpCAM的MV在患者血液中被发现以肿瘤亚型特异性的方式增强，而基质金属蛋白酶诱导因子EMMPRIN的表达独立于肿瘤类型而增加。EMMPRIN+-MV水平较高与总体存活率较低显著相关，而其他标记物仅在特定肿瘤亚组中可预测预后。通过结合所有四种肿瘤相关抗原，癌症患者与健康对照组分开，AUC高达0.85。在体外，与对照组相比，癌症患者的完整MV制剂在巨噬细胞中诱导了支持肿瘤的表型，并增加了肿瘤细胞的侵袭，这依赖于高度糖化的EMMPRIN亚型。总之，全血中T-MV的检测，即使是微量的，用标准技术是可行的，被证明是功能相关的，并与临床结果相关。
To evaluate whether tumour-derived microvesicles (T-MV), originating from the plasma membrane, represent suitable cancer biomarkers, we isolated MV from peripheral blood samples of cancer patients with locally advanced and/or metastatic solid tumours (n = 330, including 79 head & neck cancers, 74 lung cancers, 41 breast cancers, 28 colorectal cancers and 108 with other cancer forms) and controls (n = 103). Whole MV preparations were characterised using flow cytometry. While MV carrying the tumour-associated proteins MUC1, EGFR and EpCAM were found to be enhanced in a tumour-subtype-specific way in patients’ blood, expression of the matrix metalloproteinase inducer EMMPRIN was increased independent of tumour type. Higher levels of EMMPRIN+-MV correlated significantly with poor overall survival, whereas the other markers were prognostic only in specific tumour subgroups. By combining all four tumour-associated antigens, cancer patients were separated from healthy controls with an AUC of up to 0.85. Ex vivo, whole MV preparations from cancer patients, in contrast to those of controls, induced a tumour-supporting phenotype in macrophages and increased tumour cell invasion, which was dependent on the highly glycosylated isoform of EMMPRIN. In conclusion, the detection of T-MV in whole blood, even in minor amounts, is feasible with standard techniques, proves functionally relevant and correlates with clinical outcome.
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影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
通讯作者：
Théry C
影响因子：
8
作者：
Kaler, P.;Augenlicht, L.;Klampfer, L.
通讯作者：
Klampfer, L.
影响因子：
4.6
作者：
Kibria G;Ramos EK;Lee KE;Bedoyan S;Huang S;Samaeekia R;Athman JJ;Harding CV;Lötvall J;Harris L;Thompson CL;Liu H
通讯作者：
Liu H
DOI：
10.1083/jcb.131.6.1715
发表时间：
1995-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nakamura N;Rabouille C;Watson R;Nilsson T;Hui N;Slusarewicz P;Kreis TE;Warren G
通讯作者：
Warren G
影响因子：
4.4
作者：
Baj-Krzyworzeka, Monika;Szatanek, Rafal;Zembala, Marek
通讯作者：
Zembala, Marek