Involvement of eicosanoids in the pathogenesis of pancreatic cancer: The roles of cyclooxygenase-2 and 5-lipoxygenase

Figure 1 Inflammatory cell infiltration into the tumor microenvironment. As pancreatic adenocarcinoma progresses, inflammatory cells such as mast cells, neutrophils, and macrophages are attracted to the tumor microenvironment and enhance tumor growth. Leukotriene B₄ (LTB₄) is a chemotactic factor for macrophages, neutrophils, and mast cells. Fibroblasts are also activated and enhance collagen production.

Figure 2 Metabolic pathway of prostaglandins via cyclooxygenase. Arachidonic acid is released from membrane phospholipids by phospholipase A₂ and converted to PGG₂ and subsequently PGH₂ by COX. PGH₂ is then converted to PGI₂, TXA₂, PGD₂, and PGE₂. cPLA2: Cytosolic phospholipase A₂; COX: Cyclooxygenase; PG: Prostaglandin; TX: Thromboxane.

Figure 3 Metabolic pathway of arachidonic acid via 5- lipoxygenase. Arachidonic acid is released from membrane phospholipids by phospholipase A₂ and converted to 5-HPETE by 5-LOX and 5-LOX activating protein (FLAP). 5-HPETE can then form either 5-HETE or LTA₄. LTA₄ then becomes LTB₄ or LTC₄. LTC₄ can then form LTD₄ and subsequently LTE₄. cPLA2: Cytosolic phospholipase A₂; LOX: Lipoxygenase; FLAP: 5-LOX activating protein; HPETE: Hydroperoxyeicosatetraenoic acid; HETE: Hydroxyl 6 trans 8, 11, 14 cis eicosatetraenoic acid; LT: Leukotriene.