HMGB1-activated tumor-associated macrophages promote migration and invasion via NF-κB/IL-6 signaling in oral squamous cell carcinoma

Mingjing Jiang; Luyao Liu; Wei Huang; Ying Qi; Yafei Li; Bo Li

doi:10.1016/j.intimp.2023.111200

HMGB1-activated tumor-associated macrophages promote migration and invasion via NF-κB/IL-6 signaling in oral squamous cell carcinoma

Int Immunopharmacol. 2024 Jan 5:126:111200. doi: 10.1016/j.intimp.2023.111200. Epub 2023 Nov 20.

Authors

Mingjing Jiang¹, Luyao Liu², Wei Huang¹, Ying Qi¹, Yafei Li², Bo Li³

Affiliations

¹ Experimental Teaching Center, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110001, China.
² Department of Oral Anatomy and Physiology, Jilin Provincial Key Laboratory of Oral Biomedical Engineering, Hospital of Stomatology, Jilin University, Changchun 130021, China.
³ Department of Oral Anatomy and Physiology, Jilin Provincial Key Laboratory of Oral Biomedical Engineering, Hospital of Stomatology, Jilin University, Changchun 130021, China; Experimental Teaching Center, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110001, China. Electronic address: lbo@jlu.edu.cn.

PMID: 37988913
DOI: 10.1016/j.intimp.2023.111200

Abstract

Tumor-associated macrophages (TAMs) are a highly abundant cell population within the tumor microenvironment of oral squamous cell carcinomas (OSCC). Recent studies have identified an intricate cross-talk between cancer cells and macrophages in the tumor microenvironment. However, the underlying mechanism remains unclear. High-mobility group box 1 (HMGB1) was linked to metastasis and an unfavorable prognosis in head and neck squamous cell carcinoma. Furthermore, it was significantly upregulated in moderately differentiated OSCC tissues and the OSCC cell lines CAL27 and SCC9. HMGB1 knockdown impedes the ability of TAMs to induce invasion and migration of OSCC cells. Phenotypic changes in macrophages were measured after incubation of supernatant from OSCC cells transfected with HMGB1 siRNA or supplemented with recombinant HMGB1. HMGB1 induced M1 polarization of macrophages and the secretion of IL-6 via the NF-κB pathway, contributing to the OSCC malignant migration. HMGB1 originating from OSCC cells, along with its downstream signaling pathways, holds promise as a potential therapeutic target for mitigating metastasis and improving the survival rate of OSCC.

Keywords: High mobility group box-1; Invasion and migration; Tumor-associated macrophages.

MeSH terms

Carcinoma, Squamous Cell* / genetics
Cell Line, Tumor
Cell Movement
Cell Proliferation
HMGB1 Protein* / genetics
Head and Neck Neoplasms*
Humans
Interleukin-6
Mouth Neoplasms* / genetics
Mouth Neoplasms* / metabolism
Mouth Neoplasms* / pathology
NF-kappa B / metabolism
Squamous Cell Carcinoma of Head and Neck
Tumor Microenvironment
Tumor-Associated Macrophages / metabolism

Substances

NF-kappa B
Interleukin-6
HMGB1 Protein