Breast Tumor-Derived Exosomal MicroRNA-200b-3p Promotes Specific Organ Metastasis Through Regulating CCL2 Expression in Lung Epithelial Cells.
Breast Tumor-Derived Exosomal MicroRNA-200b-3p Promotes Specific Organ Metastasis Through Regulating CCL2 Expression in Lung Epithelial Cells.
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DOI：
10.3389/fcell.2021.657158
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发表时间：
2021
影响因子：
5.5
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Gu P;Sun M;Li L;Yang Y;Jiang Z;Ge Y;Wang W;Mu W;Wang H
恶性转移是乳腺癌（BC）患者死亡的最重要原因，而肺是主要的炎症和转移靶器官。外来体是纳米尺寸的囊泡，其可以被驻留细胞摄取以在肿瘤细胞优先运动之前产生转移前小生境。在本研究中，我们证明了C-C基序趋化因子配体2（CCL 2）在肺中的高表达可以募集髓源性抑制细胞（MDSC），并有助于建立微环境。CCL 2在癌条件和炎症反应下提供免疫细胞的募集。我们还建立了特异性肺内过表达CCL 2的小鼠模型，证实了BC向器官转移不是由于肿瘤细胞增殖的增强，而是由于CCL 2在靶器官的调节表达。为了更好地探索宿主组织中外泌体分子和CCL 2的串扰，我们通过外泌体静脉内注射构建了“教育”肺，并在体内测定了肺泡上皮II型细胞的显著外泌体摄取。此外，我们还发现exosomal microRNA-200 B-3 p可以与PTEN结合，可能参与AKT/NF-κB/CCL 2级联反应的调控。因此，我们的研究表明，肺中CCL 2的表达受到BC衍生的外泌体微小RNA的调节，这启动了转移前生态位，并且可能是BC肺转移发展的预后标志物。肿瘤来源的外来体诱导的向器官性和免疫抑制的示意图。
Malignant metastasis is the most important cause of death in breast cancer (BC) patients, while the lung is a major inflammation and metastatic target organ. Exosomes are nano-sized vesicles that could be uptaken by resident cells to generate the pre-metastatic niche before tumor cells preferentially motility. In the present study, we demonstrated that high expression of C-C motif chemokine ligand 2 (CCL2) in lung could recruit the myeloid-derived suppressor cells (MDSCs) and contribute to the establishment of microenvironment. CCL2 provided recruitment of immune cells under carcinomas conditions and inflammatory responses. We also developed the novel mice model for specific over-expressing CCL2 in the lung, and verified that the BC organotropic metastasis was not because of the enhanced tumor cell proliferation, but the regulatory expression of CCL2 in the target organ. To better explore the crosstalk of exosomal molecules and CCL2 in host tissue, we constructed the “education” lung by exosomes intravenous injection and determined the prominent exosome-uptake by alveolar epithelial type II cells in vivo. Furthermore, we identified the exosomal microRNA-200b-3p could bind to PTEN, which may involved in the regulation of AKT/NF-κB/CCL2 cascades. Therefore, our study suggest that CCL2 expression in the lung was regulated by BC-derived exosomal microRNA, which primed the pre-metastastatic niche and may be a prognostic marker for the development of BC lung metastasis. Schematic diagram of tumor-derived exosomes induced organotropism and immunosuppression.
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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：
2.7
作者：
Chen, Siying;Yang, Jin;Lyu, Jun
通讯作者：
Lyu, Jun
影响因子：
3.6
作者：
Jin L;Han B;Siegel E;Cui Y;Giuliano A;Cui X
通讯作者：
Cui X
影响因子：
16.6
作者：
Novo D;Heath N;Mitchell L;Caligiuri G;MacFarlane A;Reijmer D;Charlton L;Knight J;Calka M;McGhee E;Dornier E;Sumpton D;Mason S;Echard A;Klinkert K;Secklehner J;Kruiswijk F;Vousden K;Macpherson IR;Blyth K;Bailey P;Yin H;Carlin LM;Morton J;Zanivan S;Norman JC
通讯作者：
Norman JC
影响因子：
10.6
作者：
Nogués L;Benito-Martin A;Hergueta-Redondo M;Peinado H
通讯作者：
Peinado H