PGE2 (Prostaglandin E2) is a lipid mediator with key links to inflammation and cancer. PGE2 is produced by a wide variety of tissues and in several pathological conditions, including inflammation, arthritis, fever, tissue injury, endometriosis, and a variety of cancers. Recombinant prostaglandins are also used as therapy for different conditions (pulmonary hypertension, glaucoma, ulcers… even to make eyelashes grow!). So PGE2 has, as many things in life, a bright and a dark side.
Let’s talk about the dark side of PGE2 today. Reports indicate that its overexpression in cancer cells promotes angiogenesis and metastasis, by influencing the immune response (1). In brief, cyclooxygenases (COXs) convert arachidonic acid to PGE2 and thromboxane. PGE2 binds to its receptors and activates signaling pathways controlling cell proliferation, migration, apoptosis and/or angiogenesis. A few drugs are intended to target and inhibit some types of COXs, but they might have undesirable side effects and may not be efficient in some patient groups.
For example, non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib (Celebrex®), and rofecoxib (Vioxx®) in the past, have shown to possibly cause a significant increase in cardiovascular risk (2) (3).
Nevertheless, several studies highlight the need to reduce PGE2 levels in cancer, and focus on its catabolism to find new therapeutic targets (4). The COX-2/PGE2 pathway has a key influence on tumour expansion and it might even be relevant in tumour initiation (5).