Sphingosine 1-phosphate (S1P) secreted by apoptotic breast cancer cells binds to S1PR1 on tumor-associated macrophages, which induces LCN2 expression in macrophage by activating the STAT3 pathway, promoting lymphangiogenesis and metastasis of breast cancer [30] (Fig. 1C). Here, LCN2 is linked to breast carcinoma.