Prostaglandin E2 Receptor 4 (EP4) as a Therapeutic Target to Impede Breast Cancer-Associated Angiogenesis and Lymphangiogenesis

The formation of new blood (angiogenesis) and lymphatic (lymphangiogenesis) vessels are major events associated with most epithelial malignancies, including breast cancer. Angiogenesis is essential for cancer cell survival. Lymphangiogenesis critical in maintaining tumoral interstitial fluid balance importing tumor-facilitatory immune cells. Both vascular routes also serve as conduits metastasis. Intratumoral hypoxia promotes both by stimulating multiple angiogenic/lymphangiogenic growth factors. Studies on tumor-associated lymphangiogenesis its exploitation therapy have received less attention from the research community than those angiogenesis. Inflammation a key mediator processes, hijacked many cancers aberrant expression inflammation-associated enzyme cyclo-oxygenase (COX)-2. In this review, we focus showed that COX-2 promoter events, primarily resulting activation prostaglandin (PG) E receptor EP4 tumor cells, tumor-infiltrating endothelial cells; induction oncogenic microRNAs. COX-2/EP4 pathway additional progression, such migration, invasion, stimulation stem-like Based combination studies using models, show antagonists hold promise other modalities check-point inhibitors.