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

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-xB 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.