Journal Article

Extracellular vesicle IL-32 promotes the M2 macrophage polarization and metastasis of esophageal squamous cell carcinoma via FAK/STAT3 pathway

Zhou, Xiuman, Sun, Yixuan, Zhou, Xiaowen, Wu, Yahong, Zhai, Wenjie, Gao, Yanfeng, Wang, Hongfei, Shi, Chao, Zhao, Yumiao, Qian, Yuzhen, Qiu, Lu, Qi, Yuanming, Chen, Chunxia, Ning, Haoming, Han, Lu

2022

Overview

Background Metastasis is the leading cause of mortality in human cancers, including esophageal squamous cell carcinoma (ESCC). As a pro-inflammatory cytokine, IL-32 was reported to be a poor prognostic factor in many cancers. However, the role of IL-32 in ESCC metastasis remains unknown. Methods ESCC cells with ectopic expression or knockdown of IL-32 were established and their effects on cell motility were detected. Ultracentrifugation, Transmission electron microscopy and Western blot were used to verify the existence of extracellular vesicle IL-32 (EV-IL-32). Coculture assay, immunofluorescence, flow cytometry, and in vivo lung metastasis model were performed to identify how EV-IL-32 regulated the crosstalk between ESCC cells and macrophages. Results Here, we found that IL-32 was overexpressed and positively correlated to lymph node metastasis of ESCC. IL-32 was significantly higher in the tumor nest compared with the non-cancerous tissue. We found that IL-32β was the main isoform and loaded in EV derived from ESCC cells. The shuttling of EV-IL-32 derived from ESCC cells into macrophages could promote the polarization of M2 macrophages via FAK-STAT3 pathway. IL-32 overexpression facilitated lung metastasis and was positively correlated with the proportion of M2 macrophages in tumor microenvironment. Conclusions Taken together, our results indicated that EV-IL-32 derived from ESCC cell line could be internalized by macrophages and lead to M2 macrophage polarization via FAK-STAT3 pathway, thus promoting the metastasis of ESCC. These findings indicated that IL-32 could serve as a potential therapeutic target in patients with ESCC.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Apoptosis / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cell culture / Cell Line, Tumor / Chemotherapy / China / Cloning / Cytokines / Esophageal cancer / Esophageal Neoplasms - metabolism / Esophageal Neoplasms - pathology / Esophageal squamous cell carcinoma / Esophageal Squamous Cell Carcinoma - metabolism / Esophageal Squamous Cell Carcinoma - pathology / Extracellular vesicle / Extracellular vesicles / Extracellular Vesicles - metabolism / Focal Adhesion Kinase 1 - metabolism / Health aspects / Humans / IL-32 / Immunology / Interleukins - metabolism / Lung cancer / Lung Neoplasms - metabolism / Lung Neoplasms - pathology / Lung Neoplasms - secondary / M2 macrophage polarization / Macrophages / Macrophages - metabolism / Metastasis / Mortality / Oncology / Prognosis / Radiation therapy / Squamous cell carcinoma / STAT3 Transcription Factor - metabolism / Tumor Microenvironment