Molecular Mechanisms Of Cell Fusion Between Macrophages And Breast Cancer Cells Promoting Breast Cancer Proliferation And Metastasis

Breast cancer is a high-grade malignant tumor that poses a serious threat to the health of women worldwide.In recent years,the incidence of breast cancer in China has increased rapidly.The spread and distant metastasis of breast cancer are the main causes of death in patients.Studying the mechanism of breast cancer proliferation and metastasis is of great significance for the treatment and prognosis of breast cancer.Macrophages,as an important component of the tumor microenvironment,are closely related to the malignant evolution of tumor proliferation and metastasis.More and more researches suggest that cell fusion may contribute to cancer progression,including tumor initiation,reprogramming in the nucleus,and increased proliferation and metastasis.Cell fusion theory believes that the fusion cells formed by macrophages and tumor cells have the characteristics of infinite proliferation of cancer cells and easy migration of macrophages,which promotes the malignant transformation of tumors.Macrophages have strong phagocytic ability,but there is no research report on the mechanism of breast cancer proliferation and metastasis of macrophage and breast cancer cell fusion.The aim of this study was to investigate the effects of macrophage and breast cancer cell fusion on proliferation and metastasis of breast cancer and its molecular mechanisms.The results showed that the fused cells showed stronger proliferation,migration and invasion ability than the control breast cancer cells.Moreover,cell fusion promotes the development of breast cancer epithelial-mesenchymal transition(EMT)by down-regulating E-cadherin and up-regulation of N-cadherin and vimentin.We also found that macrophages fusion with breast cancer cells significantly increased the activity of TCF/LEF transcription factor in the Wnt/β-catenin pathway and up-regulated its downstream target genes cyclin D1,c-Myc.Furthermore,the fused cells showed no change in total PI3 K and AKT expression but a significant increase in p-PI3 K and p-AKT phosphorylation levels compared to control breast cancer cells.The fused cells and breast cancer cells were then treated with the PI3 K specific inhibitor LY294002 and the results showed that LY294002 inhibited the activation of p-PI3 K and p-AKT expression.In conclusion,our treatment indicates that fusion of macrophages with breast cancer cells may promote proliferation,migration and invasion of breast cancer cells by activating Wnt/β-catenin,a PI3K/AKT signaling pathway.This research will help to elucidate of cell fusion in the mechanism of cancer occurrence and metastasis,in order to provide new strategies for the treatment of breast cancer.