High TSPAN8 expression in epithelial cancer cell-derived small extracellular vesicles promote confined diffusion and pronounced uptake.
High TSPAN8 expression in epithelial cancer cell-derived small extracellular vesicles promote confined diffusion and pronounced uptake.
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上皮癌细胞来源的小细胞外囊泡中的高 TSPAN8 表达促进有限扩散和明显摄取。
DOI：
10.1002/jev2.12167
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发表时间：
2021-11
影响因子：
16
通讯作者：
Yue S
中科院分区：
文献类型：
--
作者：
Wang T;Wang X;Wang H;Li L;Zhang C;Xiang R;Tan X;Li Z;Jiang C;Zheng L;Xiao L;Yue S
小细胞外囊泡（sEVs）在细胞间通讯中起着关键作用。由sEV携带的货物分子可以影响受体细胞的表型和功能。上皮癌细胞来源的sEV，特别是富含CD 151或四跨膜蛋白8（TSPAN 8）和相关整合素的sEV，可促进肿瘤进展。sEV与受体细胞的结合和调节机制仍然难以捉摸。在这里，我们使用基因工程乳腺癌细胞来获得富含TSPAN 8的sEV，并评估了TSPAN 8对靶细胞膜扩散和转运特性的影响。单粒子追踪技术显示TSPAN 8通过受限扩散显著促进sEV结合。功能测定表明，转基因TSPAN 8-sEV货物增加了癌细胞运动性和上皮-间质转化（EMT）。在体内，转基因TSPAN 8-sEV促进了sEV在肝、肺和脾中的摄取。我们得出结论，TSPAN 8通过强制限制扩散促进sEV-靶细胞相互作用，并显著增加细胞运动性。因此，TSPAN 8 ‐sEV可能是一个重要的直接或间接治疗靶点。
Small extracellular vesicles (sEVs) play a key role in intercellular communication. Cargo molecules carried by sEVs may affect the phenotype and function of recipient cells. Epithelial cancer cell‐derived sEVs, particularly those enriched in CD151 or tetraspanin8 (TSPAN8) and associated integrins, promote tumour progression. The mechanism of binding and modulation of sEVs to recipient cells remains elusive. Here, we used genetically engineered breast cancer cells to derive TSPAN8‐enriched sEVs and evaluated the impact of TSPAN8 on target cell membrane's diffusion and transport properties. The single‐particle tracking technique showed that TSPAN8 significantly promoted sEV binding via confined diffusion. Functional assays indicated that the transgenic TSPAN8‐sEV cargo increased cancer cell motility and epithelial‐mesenchymal transition (EMT). In vivo, transgenic TSPAN8‐sEV promoted uptake of sEVs in the liver, lung, and spleen. We concluded that TSPAN8 encourages the sEV‐target cell interaction via forced confined diffusion and significantly increases cell motility. Therefore, TSPAN8‐sEV may serve as an important direct or indirect therapeutic target.
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影响因子：
5.2
作者：
El Kharbili，Manale;Cario，Muriel;Berthier-Vergnes，Odile
通讯作者：
Berthier-Vergnes，Odile
影响因子：
17.1
作者：
Hu, Shiqi;Li, Zhenhua;Cheng, Ke
通讯作者：
Cheng, Ke
影响因子：
8
作者：
Park, C. S.;Kim, T-K;Lee, S.
通讯作者：
Lee, S.
影响因子：
13.6
作者：
Liu, Yang;Fan, Jia;Hu, Tony Y.
通讯作者：
Hu, Tony Y.
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