癌相关成纤维细胞(CAFs)在癌症进展中起着重要作用。唾液腺腺样囊性癌(SACC)具有高侵袭和转移的倾向。了解CAFs如何与SACC细胞相互作用对于开发针对SACC的新靶向疗法至关重要。胞外囊泡(EVs)在细胞间的通讯中发挥着重要作用。然而，CAFs来源的EVs在SACC侵袭中的作用仍不清楚。为了表明CAFs EVs参与了SACC的EMT并促进了肿瘤侵袭，我们使用了西方印迹和透射电子显微镜来表征CAFs源EVs。研究CAFs-EVs对肿瘤细胞的生物基础，包括愈合伤口试验和Transwell试验。我们应用RNA干扰转染、Western印迹、愈合伤口和Transwell试验来研究CAFs-EVs中IL6对SACC细胞的影响及其机制。采用皮下异种移植模型评估CAFs在体内诱导SACC的EMT。我们发现，CAFs EVs促进了SACC细胞的迁移和侵袭。与阴性对照组相比，用CAFs EVs处理的SACC细胞表皮间充质转化(EMT)的生物标志物表达更高，而CAFs及其EVs中检测到了高水平的IL6。CAFs中IL6的沉默降低了CAFs EVs诱导的SACC细胞组织侵袭性和EMT生物标志物表达。CAFs EV相关的IL6通过激活JAK2/STAT3信号通路促进SACC EMT。CAFs来源EVs通过激活JAK2/STAT3信号通路携带IL6以促进SACC EMT。版权所有©2022墨西哥社会保险机构(IMSS)。由Elsevier Inc.出版。保留所有权利。

Carcinoma-associated fibroblasts (CAFs) play a pivotal role in cancer progression. Salivary adenoid cystic carcinoma (SACC) has a high tendency to invade and metastasize. Understanding how CAFs interact with SACC cells is essential for developing new targeted therapies for SACC. Extracellular vesicles (EVs) play important roles in intercellular communication. However, the role of CAFs-derived EVs in SACC invasion remains poorly understood.To show that CAFs EVs are involved in the EMT of SACC and promote tumor invasion.CAFs-derived EVs were characterized by western blot and transmission electron microscopy. Wound healing and transwell assay were performed for assessing biological foundation of CAFs-EVs for tumor cells. RNA interference transfection, western blot, wound healing and transwell assay were applied to study the effect of IL6 from CAFs-EVs on SACC cells and the mechanism. A subcutaneous xenograft model was used to evaluate the EMT of SACC induced by CAFs in vivo.In this study, we show that CAFs EVs promote the migration and invasion of SACC cells. The expression of biomarkers of epithelial-mesenchymal transition (EMT) was higher in SACC cells treated with CAFs EVs than in the negative controls, and high levels of IL6 were detected in CAFs and their EVs. Knockdown of IL6 in CAFs decreased tissue invasiveness and EMT biomarker expression in SACC cells induced by CAFs EVs. CAFs EV-associated IL6 promoted SACC EMT by activating the JAK2/STAT3 signaling pathway.CAFs-derived EVs carry IL6 to improve EMT of SACC by activating the JAK2/STAT3 signaling pathway.Copyright © 2022 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.