Extracellular Vesicles from Carcinoma-associated Fibroblasts Promote EMT of Salivary Adenoid Cystic Carcinoma Via IL-6

被引：7
作者：
Al-raimi, Hyat Ahmed Ibrahim [1 ]
Kong, Jing [1 ]
Ran, Yan [1 ]
Zhu, Lei [1 ]
Li, Jiao [1 ,2 ,3 ,4 ]
Liu, Xue [1 ,2 ,3 ,4 ]
Yang, Xuesong [5 ]
Qi, Dongyuan [6 ]
Liu, Tingjiao [1 ,2 ,3 ,4 ]
机构：
[1] Dalian Med Univ, Sch Stomatol, Dept Oral Pathol, Dalian, Peoples R China
[2] Fudan Univ, Shanghai Stomatol Hosp, Dept Oral Pathol, Tianjin Rd 2, Shanghai 200001, Peoples R China
[3] Fudan Univ, Sch Stomatol, Tianjin Rd 2, Shanghai 200001, Peoples R China
[4] Fudan Univ, Shanghai Key Lab Craniomaxillofacial Dev & Dis, Shanghai, Peoples R China
[5] Dalian Med Univ, Dept Biochem & Mol Biol, Liaoning Prov Core Lab Glycobiol & Glycoengineerin, Dalian, Peoples R China
[6] Dalian Med Univ, Affiliated Hosp 1, Dept Oral Surg, Dalian, Peoples R China
来源：
ARCHIVES OF MEDICAL RESEARCH | 2023年 / 54卷 / 01期
基金：
中国国家自然科学基金;
关键词：
Salivary adenoid cystic carcinoma; Carcinoma-associated fibroblasts; Extracellular vesicles; Epithelial-mesenchymal transition; Interleukin; 6; TO-MESENCHYMAL TRANSITION; CANCER; METASTASIS; EXOSOMES; INVASION; CHEMORESISTANCE; PROGRESSION; ACTIVATION; EXPRESSION; MIGRATION;
D O I：
10.1016/j.arcmed.2022.12.005
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Background. Carcinoma-associated fibroblasts (CAFs) play a pivotal role in cancer pro-gression. Salivary adenoid cystic carcinoma (SACC) has a high tendency to invade and metastasize. Understanding how CAFs interact with SACC cells is essential for devel-oping 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.Aim of the Study. To show that CAFs EVs are involved in the EMT of SACC and promote tumor invasion.Methods. CAFs-derived EVs were characterized by western blot and transmission elec-tron microscopy. Wound healing and transwell assay were performed for assessing bio-logical 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.Results. 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 con-trols, 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. Conclusion. CAFs-derived EVs carry IL6 to improve EMT of SACC by activating the JAK2/STAT3 signaling pathway.(c) 2022 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.
引用
收藏
页码：27 / 36
页数：10
相关论文
共 52 条
[1]   The Role of the IL-6 Cytokine Family in Epithelial-Mesenchymal Plasticity in Cancer Progression [J].
Abaurrea, Andrea ;
Araujo, Angela M. ;
Caffarel, Maria M. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (15)
[2]   Fibroblasts in the Tumor Microenvironment: Shield or Spear? [J].
Alkasalias, Twana ;
Moyano-Galceran, Lidia ;
Arsenian-Henriksson, Marie ;
Lehti, Kaisa .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (05)
[3]   Adipocyte-Derived Fibroblasts Promote Tumor Progression and Contribute to the Desmoplastic Reaction in Breast Cancer [J].
Bochet, Ludivine ;
Lehuede, Camille ;
Dauvillier, Stephanie ;
Wang, Yuan Yuan ;
Dirat, Beatrice ;
Laurent, Victor ;
Dray, Cedric ;
Guiet, Romain ;
Maridonneau-Parini, Isabelle ;
Le Gonidec, Sophie ;
Couderc, Bettina ;
Escourrou, Ghislaine ;
Valet, Philippe ;
Muller, Catherine .
CANCER RESEARCH, 2013, 73 (18) :5657-5668
[4]   Biological heterogeneity and versatility of cancer-associated fibroblasts in the tumor microenvironment [J].
Bu, Luke ;
Baba, Hideo ;
Yoshida, Naoya ;
Miyake, Keisuke ;
Yasuda, Tadahito ;
Uchihara, Tomoyuki ;
Tan, Patrick ;
Ishimoto, Takatsugu .
ONCOGENE, 2019, 38 (25) :4887-4901
[5]   Tumor-associated stromal cells as key contributors to the tumor microenvironment [J].
Bussard, Karen M. ;
Mutkus, Lysette ;
Stumpf, Kristina ;
Gomez-Manzano, Candelaria ;
Marini, Frank C. .
BREAST CANCER RESEARCH, 2016, 18
[6]   Effect of survivin downregulation by simvastatin on the growth and invasion of salivary adenoid cystic carcinoma [J].
Cai, Wen-Yan ;
Zhuang, Ying ;
Yan, Fei ;
Li, Ting ;
Song, Wen-Ting ;
Sun, Jin-Hu .
MOLECULAR MEDICINE REPORTS, 2018, 18 (02) :1939-1946
[7]   Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts [J].
Calvo, Fernando ;
Ege, Nil ;
Grande-Garcia, Araceli ;
Hooper, Steven ;
Jenkins, Robert P. ;
Chaudhry, Shahid I. ;
Harrington, Kevin ;
Williamson, Peter ;
Moeendarbary, Emad ;
Charras, Guillaume ;
Sahai, Erik .
NATURE CELL BIOLOGY, 2013, 15 (06) :637-+
[8]   Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b [J].
Chen, Y. ;
Zeng, C. ;
Zhan, Y. ;
Wang, H. ;
Jiang, X. ;
Li, W. .
ONCOGENE, 2017, 36 (33) :4692-4705
[9]   Galectin-1 from cancer-associated fibroblasts induces epithelial-mesenchymal transition through β1 integrin-mediated upregulation of Gli1 in gastric cancer [J].
Chong, Yang ;
Tang, Dong ;
Xiong, Qingquan ;
Jiang, Xuetong ;
Xu, Chuanqi ;
Huang, Yuqin ;
Wang, Jie ;
Zhou, Huaicheng ;
Shi, Youquan ;
Wu, Xiaoqing ;
Wang, Daorong .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2016, 35 :1-13
[10]   Intrinsic and Extrinsic Modulators of the Epithelial to Mesenchymal Transition: Driving the Fate of Tumor Microenvironment [J].
D'Angelo, Edoardo ;
Lindoso, Rafael Soares ;
Sensi, Francesca ;
Pucciarelli, Salvatore ;
Bussolati, Benedetta ;
Agostini, Marco ;
Collino, Federica .
FRONTIERS IN ONCOLOGY, 2020, 10
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