Taken together, we conclude that the crosstalk between cancer cells and LECs via VEGF-C/VEGFR3 and chemokine/CXCR2 signaling plays a pivotal role for the establishment of lymphovascular niches, and CXCR2 may be a target for the inhibition of lymphatic metastasis and for the re-activation of anti-cancer immunity in breast cancer. Here, FLT4 is linked to breast cancer.