Human liver stem cell-derived microvesicles inhibit hepatoma growth in SCID mice by delivering antitumor microRNAs.
Human liver stem cell-derived microvesicles inhibit hepatoma growth in SCID mice by delivering antitumor microRNAs.
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DOI：
10.1002/stem.1161
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发表时间：
2012-09
期刊：
影响因子：
5.2
通讯作者：
Camussi, Giovanni
中科院分区：
文献类型：
--
作者：
Fonsato, Valentina;Collino, Federica;Herrera, Maria Beatriz;Cavallari, Claudia;Deregibus, Maria Chiara;Cisterna, Barbara;Bruno, Stefania;Romagnoli, Renato;Salizzoni, Mauro;Tetta, Ciro;Camussi, Giovanni
微囊泡（Microvesicles，MV）在细胞间通讯中起着重要作用。最近的研究表明，MV可以在细胞之间传递遗传信息。在这里，我们表明，来自人成体肝干细胞（HLSC）的MV可以在体外重编程HepG 2肝癌和原发性肝癌细胞通过抑制它们的生长和存活。体内瘤内给予MV可诱导SCID小鼠中发生的异位肿瘤消退。基于以下证据，我们认为其作用机制与从HLSC衍生的MV（MV-HLSC）向肿瘤细胞递送microRNA（miRNAs）有关：（a）在HepG 2中，MV-HLSC的快速、CD 29介导的内化和MV摄取后肿瘤细胞生长的抑制;（B）MV-HLSC转移具有潜在抗肿瘤活性的miRNA，所述miRNA相对于正常肝细胞在HepG 2细胞中下调;（c）在用RNA酶MV预处理或产生耗尽miRNA的MV后MV-HLSC抗肿瘤作用的消除;（d）通过用miRNA模拟物抑制HepG 2来证明所选miRNA的相关性。MV-HLSC的抗肿瘤作用也在肝脏以外的肿瘤中观察到，如淋巴母细胞瘤和胶质母细胞瘤。这些结果表明，通过来源于干细胞的MV递送选定的miRNA可以抑制肿瘤生长并刺激凋亡。干细胞2012;30：1985-1998
Microvesicles (MVs) play a pivotal role in cell-to-cell communication. Recent studies demonstrated that MVs may transfer genetic information between cells. Here, we show that MVs derived from human adult liver stem cells (HLSC) may reprogram in vitro HepG2 hepatoma and primary hepatocellular carcinoma cells by inhibiting their growth and survival. In vivo intratumor administration of MVs induced regression of ectopic tumors developed in SCID mice. We suggest that the mechanism of action is related to the delivery of microRNAs (miRNAs) from HLSC-derived MVs (MV-HLSC) to tumor cells on the basis of the following evidence: (a) the rapid, CD29-mediated internalization of MV-HLSC in HepG2 and the inhibition of tumor cell growth after MV uptake; (b) the transfer by MV-HLSC of miRNAs with potential antitumor activity that was downregulated in HepG2 cells with respect to normal hepatocytes; (c) the abrogation of the MV-HLSC antitumor effect after MV pretreatment with RNase or generation of MVs depleted of miRNAs; (d) the relevance of selected miRNAs was proven by transfecting HepG2 with miRNA mimics. The antitumor effect of MV-HLSC was also observed in tumors other than liver such as lymphoblastoma and glioblastoma. These results suggest that the delivery of selected miRNAs by MVs derived from stem cells may inhibit tumor growth and stimulate apoptosis. Stem Cells2012;30:1985–1998
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影响因子：
8
作者：
Bourguignon, L. Y. W.;Earle, C.;Wong, G.;Spevak, C. C.;Krueger, K.
通讯作者：
Krueger, K.
影响因子：
11.2
作者：
Katakowski M;Buller B;Wang X;Rogers T;Chopp M
通讯作者：
Chopp M
影响因子：
3.7
作者：
Collino F;Deregibus MC;Bruno S;Sterpone L;Aghemo G;Viltono L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
20.3
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
15.3
作者：
LEHMANN, V;FREUDENBERG, MA;GALANOS, C
通讯作者：
GALANOS, C