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. SCC7 cells and Raw 264.7 cells were fused in vitro to generate fusion cells.Total RNA was extracted fromSCC7 cells, Raw 264.7 cells and fusion cells.

肿瘤转移是口腔鳞状细胞癌（Oral Squamous Cell Carcinoma，OSCC）患者高死亡率的核心诱因。尽管已有诸多假说试图阐释肿瘤转移的发生机制，但转移性肿瘤细胞的起源仍未明确。本研究旨在探究细胞融合在OSCC转移性肿瘤细胞形成过程中的作用。本研究通过体外融合小鼠源OSCC肿瘤细胞与巨噬细胞，并对比了融合细胞与亲本细胞的增殖、迁移及吞噬能力。随后，本研究对比了融合细胞与亲本细胞的转录组差异。最后，本研究分析了融合细胞与OSCC患者预后之间的关联。本研究成功在体外实现了小鼠源OSCC肿瘤细胞与巨噬细胞的融合。细胞学与分子实验结果显示，OSCC肿瘤细胞与巨噬细胞融合后，获得了与迁移相关的表型；且融合细胞的迁移能力与"趋化因子信号通路"的激活密切相关。此外，本研究证实，OSCC肿瘤组织中融合细胞的存在与淋巴结转移及不良预后显著相关。OSCC肿瘤细胞与巨噬细胞融合后，其体内的趋化因子信号通路被激活，进而促进肿瘤转移。本研究通过体外融合SCC7细胞与Raw 264.7细胞获得融合细胞，并分别从SCC7细胞、Raw 264.7细胞及融合细胞中提取总RNA。