Fig. 11

Proposed roles of PGE2-EP4 in breast cancer associated lymphangiogenesis. Molecular cross-talk amongst tumor cells, host cells (macrophages) and LECs: Both tumor and host cells produce PGE2 and VEGF-C/D. PGE2 binding to EP4 receptors on LEC directly promote lymphangiogenesis (via proliferation migration and tubulogenesis) following activation of PI3K/Akt and Erk signaling. EP4 activation also upregulates VEGF-D production by the LEC. VEGF-C/D derived from multiple sources (autocrine and paracrine) stimulates sprouting of new lymphatic vessels by binding to VEGFR-3 on LEC