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

Hyat Ahmed Ibrahim Al-Raimi; Jing Kong; Yan Ran; Lei Zhu; Jiao Li; Xue Liu; Xuesong Yang; Dongyuan Qi; Tingjiao Liu

doi:10.1016/j.arcmed.2022.12.005

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

Arch Med Res. 2023 Jan;54(1):27-36. doi: 10.1016/j.arcmed.2022.12.005. Epub 2022 Dec 20.

Authors

Hyat Ahmed Ibrahim Al-Raimi¹, Jing Kong¹, Yan Ran¹, Lei Zhu¹, Jiao Li², Xue Liu², Xuesong Yang³, Dongyuan Qi⁴, Tingjiao Liu⁵

Affiliations

¹ Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian, China.
² Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian, China; Department of Oral Pathology, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, China; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China.
³ Department of Biochemistry and Molecular Biology, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian Medical University, Dalian, China.
⁴ Department of Oral Surgery, the First Affiliated Hospital, Dalian Medical University, Dalian, China.
⁵ Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian, China; Department of Oral Pathology, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, China; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China. Electronic address: tingjiao_liu@fudan.edu.cn.

PMID: 36543625
DOI: 10.1016/j.arcmed.2022.12.005

Abstract

Background: 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.

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 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.

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 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.

Conclusion: CAFs-derived EVs carry IL6 to improve EMT of SACC by activating the JAK2/STAT3 signaling pathway.

Keywords: Carcinoma-associated fibroblasts; Epithelial-mesenchymal transition; Extracellular vesicles; Interleukin 6; Salivary adenoid cystic carcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Carcinoma, Adenoid Cystic* / genetics
Carcinoma, Adenoid Cystic* / metabolism
Carcinoma, Adenoid Cystic* / pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Epithelial-Mesenchymal Transition
Extracellular Vesicles* / metabolism
Extracellular Vesicles* / pathology
Fibroblasts / metabolism
Fibroblasts / pathology
Humans
Interleukin-6 / genetics
Interleukin-6 / metabolism
Neoplasm Invasiveness

Substances

Interleukin-6
Biomarkers