Primary tumor-derived exosomes facilitate metastasis by regulating adhesion of circulating tumor cells via SMAD3 in liver cancer.
Primary tumor-derived exosomes facilitate metastasis by regulating adhesion of circulating tumor cells via SMAD3 in liver cancer.
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原发肿瘤来源的外泌体通过 SMAD3 调节肝癌循环肿瘤细胞的粘附，促进转移
DOI：
10.1038/s41388-018-0391-0
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发表时间：
2018-11
期刊：
影响因子：
8
通讯作者：
Liang T
中科院分区：
文献类型：
--
作者：
Fu Q;Zhang Q;Lou Y;Yang J;Nie G;Chen Q;Chen Y;Zhang J;Wang J;Wei T;Qin H;Dang X;Bai X;Liang T
肝细胞癌（HCC）是一种致死性疾病，HCC患者经常死于转移。肝癌转移的机制尚不完全清楚。在本研究中，在体外和体内数据表明，肝癌细胞促进癌细胞增殖和肺转移的形成，在旁分泌/内分泌的方式。我们发现HCC衍生的外泌体介导了这种现象，并观察到在这些恶性外泌体存在下增强的细胞粘附。我们进一步确定了活性氧（ROS）调节粘附分子。有趣的是，附着的HCC细胞释放含有SMAD家族成员3（SMAD 3）蛋白和mRNA的外泌体，这些外泌体被递送到分离的HCC细胞并促进它们的粘附。这些外泌体在受体HCC细胞中诱导增强的SMAD 3信号传导并增加其粘附能力。此外，我们发现肝癌患者外周血中存在SMAD 3丰富的外泌体，其水平与疾病分期和原发肿瘤的SMAD 3表达相关。我们的研究提出了原发性HCC支持转移形成的可能机制，并揭示了SMAD 3在外泌体介导的原发性和循环HCC细胞之间的串扰中的作用。
Hepatocellular carcinoma (HCC) is a fatal disease and patients with HCC frequently die from metastasis. The mechanisms of HCC metastasis are not completely understood. In the present study, in vitro and in vivo data showed that HCC cells promoted cancer cell proliferation and lung metastases formation in a paracrinal/endocrinal way. We found that HCC-derived exosomes mediated this phenomenon and observed enhanced cell adhesion in the presence of these malignant exosomes. We further identified that reactive oxygen species (ROS) regulated the adhesive molecules. Intriguingly, attached HCC cells released exosomes containing both SMAD Family Member 3 (SMAD3) protein and mRNA, which were delivered to detached HCC cells and facilitated their adhesion. These exosomes induced enhanced SMAD3 signaling in the recipient HCC cells and increased their adhesive ability. In addition, we showed that SMAD3-abundant exosomes existed in the peripheral blood of patients with HCC, and their levels correlated with disease stage and the SMAD3 expression of primary tumors. Our study suggested a possible mechanism by which primary HCC supported metastases formation and revealed the role of SMAD3 in the exosomes-mediated crosstalk between primary and circulating HCC cells.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
8
作者：
Ren, T.;Zhang, H.;Xing, J.
通讯作者：
Xing, J.
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：
4.7
作者：
He, Mian;Qin, Hao;Wong, Nathalie
通讯作者：
Wong, Nathalie
影响因子：
9.6
作者：
SLOOTER, GD;MARQUET, RL;IJZERMANS, JNM
通讯作者：
IJZERMANS, JNM