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Published in: Pediatric Surgery International 1/2023

01-12-2023 | Original Article

Potential involvement of IL-32 in cell-to-cell communication between macrophages and hepatoblastoma

Authors: Ahmad Adawy, Lianbo Li, Hiroki Hirao, Tomoaki Irie, Daiki Yoshii, Hiromu Yano, Yukio Fujiwara, Shigeyuki Esumi, Masaki Honda, Shinya Suzu, Yoshihiro Komohara, Taizo Hibi

Published in: Pediatric Surgery International | Issue 1/2023

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Abstract

Purpose

This study investigated the expression of interleukin 32 (IL-32) in hepatoblastoma, the most common primary pediatric liver tumor, and its possible roles in tumorigenesis.

Methods

IL-32 expression was investigated in two hepatoblastoma cell lines (Hep G2 and HuH 6) in the steady state and after co-culture with macrophages by RNA-seq analysis and RT-qPCR, and after stimulation with chemotherapy. Cultured macrophages were stimulated by IL-32 isoforms followed by RT-qPCR and western blot analysis. IL-32 immunohistochemical staining (IHC) was performed using specimens from 21 hepatoblastoma patients. Clustering analysis was also performed using scRNA-seq data downloaded from Gene Expression Omnibus.

Results

The IL-32 gene is expressed by hepatoblastoma cell lines; expression is upregulated by paracrine cell–cell communication with macrophages, also by carboplatin and etoposide. IL-32 causes protumor activation of macrophages with upregulation of PD-L1, IDO-1, IL-6, and IL-10. In the patient pool, IHC was positive only in 48% of cases. However, in the downloaded dataset, IL-32 gene expression was negative.

Conclusion

IL-32 was detected in hepatoblastoma cell lines, but not in all hepatoblastoma patients. We hypothesized that stimulation such as chemotherapy might induce expression of IL-32, which might be a critical mediator of chemoresistance in hepatoblastoma through inducing protumor activation in macrophages.
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Metadata
Title
Potential involvement of IL-32 in cell-to-cell communication between macrophages and hepatoblastoma
Authors
Ahmad Adawy
Lianbo Li
Hiroki Hirao
Tomoaki Irie
Daiki Yoshii
Hiromu Yano
Yukio Fujiwara
Shigeyuki Esumi
Masaki Honda
Shinya Suzu
Yoshihiro Komohara
Taizo Hibi
Publication date
01-12-2023
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Surgery International / Issue 1/2023
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-023-05557-0

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