细胞外囊泡（EVs）通过运输生物活性分子，代表了一种最近发现的细胞间通讯的方式。最近有证据表明，癌瘤干细胞（CSCs）分泌的EVs对癌症发生和转移起着重要贡献。本研究旨在探索CSCs-EVs在胃癌（GC）内部信号网络中介导的可能分子机制。从GC细胞中分离CSCs和非干细胞癌细胞（NSCCs），并从CSCs中分离出EVs。通过RNA干扰技术抑制CSCs中的H19，并将CSCs-EVs或含有shRNA-H19的CSCs-EVs（CSCs-EVs-sh-H19）与NSCCs共培养，然后评估NSCCs的恶性行为和干细胞特性。建立GC小鼠模型，将体内处理过sh-H19的NSCCs释放的CSCs-EVs注入小鼠模型。CSCs与NSCCs相比拥有显著的自我更新和致瘤能力。CSCs通过分泌EVs促进NSCCs的恶性行为和干细胞特性标记蛋白的表达。限制CSCs-EVs的分泌会抑制NSCCs的在体肿瘤生成和转移。CSCs-EVs可以将H19传递到NSCCs中。H19促进NSCCs的恶性行为和干细胞特性标志蛋白在体内外的表达，同时与YAP/CDX2信号轴的激活机制相关。总之，本研究指出了CSCs-EVs在GC中的致癌和转移潜力中H19/YAP/CDX2的新型调节轴的重要性，并可能成为抗癌治疗的潜在靶点。©2023年作者。

Extracellular vesicles (EVs) transport biologically active molecules, and represent a recently identified way of intercellular communication. Recent evidence has also reported that EVs shed by cancer stem cells (CSCs) make a significant contribution to carcinogenesis and metastasis. Here, this study aims to explore the possible molecular mechanism of CSCs-EVs in gastric cancer (GC) by mediating intratumor communication network.CSCs and non-stem cancer cells (NSCCs) were sorted from GC cells, and EVs were isolated from CSCs. H19 was knocked down in CSCs, and CSCs-EVs or CSCs-EVs containing shRNA-H19 (CSCs-EVs-sh-H19) were co-cultured with NSCCs, followed by evaluation of the malignant behaviors and stemness of NSCCs. Mouse models of GC were established and injected with CSCs-EVs from sh-H19-treated NSCCs in vivo.CSCs had notable self-renewal and tumorigenic capacity compared with NSCCs. CSCs promoted the malignant behaviors of NSCCs and expression of stemness marker proteins through secretion of EVs. Inhibited secretion of CSCs-EVs curtailed the tumorigenicity and metastasis of NSCCs in vivo. H19 could be delivered by CSCs-EVs into NSCCs. H19 promoted the malignant behaviors of NSCCs and stemness marker protein expression in vitro along with tumorigenicity and liver metastasis in vivo, which was mechanistically associated with activation of the YAP/CDX2 signaling axis.Taken together, the present study points to the importance of a novel regulatory axis H19/YAP/CDX2 in carcinogenic and metastatic potential of CSCs-EVs in GC, which may be potential targets for anticancer therapy.© 2023. The Author(s).