PGE2 mediated EP4 activation on cancer or host cells resulting from aberrant COX-2 activity was shown to promote multiple cellular events responsible for breast cancer progression: paralysis of host anti-tumor immune cells16,17, stimulation of tumor cell migration and invasiveness18,19, tumor-associated angiogenesis and lymphangiogenesis resulting from upregulation of lymphangiogenic factors VEGF-C or VEGF-D in cancer cells20–22 or tumor-infiltrating macrophages22, and finally, an induction of stem-like cells (SLC) phenotype23,24. Here, VEGFD is linked to neoplasm.