School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin, China.
J Extracell Vesicles. 2021 Nov;10(13):e12167. doi: 10.1002/jev2.12167.
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.
细胞外小泡（sEVs）在细胞间通讯中发挥着关键作用。sEV 携带的货物分子可能影响受体细胞的表型和功能。上皮癌细胞来源的 sEVs，特别是富含 CD151 或四跨膜蛋白 8（TSPAN8）和相关整合素的 sEVs，促进肿瘤进展。sEV 与受体细胞结合和调节的机制仍不清楚。在这里，我们使用基因工程乳腺癌细胞衍生出富含 TSPAN8 的 sEVs，并评估了 TSPAN8 对靶细胞膜扩散和转运特性的影响。单颗粒跟踪技术显示，TSPAN8 通过受限扩散显著促进 sEV 的结合。功能分析表明，转基因 TSPAN8-sEV 货物增加了癌细胞的迁移和上皮-间充质转化（EMT）。在体内，转基因 TSPAN8-sEV 促进了 sEV 在肝脏、肺和脾脏中的摄取。我们得出结论，TSPAN8 通过强制受限扩散促进 sEV-靶细胞相互作用，并显著增加细胞迁移。因此，TSPAN8-sEV 可能是一个重要的直接或间接的治疗靶点。
