CCL2 and breast cancer: Since we have found E2 could directly increase CCL2 expression in ER+ breast cancer cells, and CCL2-CCR2 axis also coordinated breast cancer cell viability, migration and invasion in vitro as shown in Supplementary Fig. S1, which was consistent with a previous study reported by Fang W. B. et al. 11, further experiments were conducted to verify how estrogen exposure affected biological functions of breast cancer cell and whether CCL2-CCR2 axis involved in it.