Cell fusion between tumor cells and macrophages promotes the metastasis of OSCC patient through the activation of the chemokine signaling pathway

Tumor metastasis is responsible for the high mortality rate of patients with oral squamous cell carcinoma (OSCC). Although many hypotheses have been proposed to elucidate the mechanism of tumor metastasis, the origin of the metastatic tumor cells remains unclear. In this study, we explored the role of cell fusion in the formation of OSCC metastatic tumor cells. Murine OSCC tumor cells and macrophages were fused in vitro, and the cell proliferation, migration, and phagocytosis abilities of hybrid cells and parental cells were compared. Subsequently, we compared the transcriptome differences between hybrid and parental cells. Finally, we observed an association between the hybrid cells and the prognosis of patients with OSCC. Murine OSCC tumor cells and macrophages were successfully fused in vitro. The cytological and molecular experimental results revealed that OSCC tumor cells obtained a migration-related phenotype after fusion with macrophages, and the migration ability of hybrid cells was related to the activation of the “chemokine signal pathway”. Moreover, we proved that the existence of hybrid cells in OSCC tumor tissues is closely related to lymph node metastasis and poor prognosis. After fusion with macrophages, the chemokine signaling pathway in OSCC tumor cells was activated, leading to metastasis.