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

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.

• 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
• Journal: Pediatric surgery international (Pediatr Surg Int) Vol. 39 Issue 1 Pg. 275 (Sep 26 2023) ISSN: 1437-9813 [Electronic] Germany
• PMID: 37751001 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Interleukins
• IL32 protein, human

Topics

• Humans
• Blotting, Western
• Cell Communication
• Hepatoblastoma (genetics)
• Interleukins (genetics)
• Liver Neoplasms (genetics)