mice. These studies are interpreted as indicating that EP4 plays both protective and damaging roles in the heart with the protective effects of EP4 due at least in part to its ability to suppress inflammation. Lipid metabolism EP4 receptor-depleted mice exhibit slower weight gain; reduced adiposity upon high fat diet challenge; and shortened life span. These deficiencies are associated with disrupted lipid metabolism due to impaired triglyceride clearance; this impaired triglyceride clearance may underlie the cited deficiencies. Cancer The EP4 receptor is over-expressed in human prostate cancer tissue and a selective EP4-receptor antagonist inhibits the growth and metastasis of human prostate cancer cell xenografts. An EP4 receptor antagonist as well EP4 Gene knockdown inhibit the in vitro proliferation and invasiveness of human breast cancer cells. And, gene knockdown of EP4 inhibit the metastasis of murine breast cancer cells in a mouse model of induced breast cancer. PGE2 stimulates the in vitro growth of human non-small cell lung cancer while an antagonist of EP4 or EP4 gene knockdown inhibits this growth. These results indicate that the stimulation of EP4 promotes the growth of various types of cancer cells and therefore may play a role in the progression of certain types of human cancer. Hearing EP44 receptors are expressed in the cochlea of the inner ear. Pre- and post-treatment of guinea pigs with an EP4 agonist significantly attenuated threshold shifts of auditory brain stem responses and significantly reduced the loss of outer hair cells caused by prior noise exposure. These findings indicate that EP4 is involved in mechanisms for prostaglandin E(1) actions on the cochlea, and local EP4 agonist treatment may be a means for attenuating noise-induced hearing lose. Eye A selective EP4 antagonists significantly reduced corneal neovascularization in rats caused by oxygen-induced retinopathy or laser-induced choroidal neovascularization. This result suggests that EP4 activation contributes to corneal neovascularization and that EP4 antagonists may be useful for treating neovascular eye disease. Clinical significance Translational research Clinical translational research studies using EP4 stimulators (i.e. agonists) or inhibitors (i.e. antagonists) that have been conducted or are underway include: The selective EP4 agonist, (ONO-4819), improved the ulcerative colitis symptoms of 3 among 4 tested patients in a phase 2 clinical trial finished in 2009 (https://clinicaltrials.gov/ct2/show/record/NCT00296556?term=rivenprost&rank=10) but no follow-up studies have been recorded. The EP4 selective antagonist, CJ-023,423, was tested for its effectiveness in treating gastroduodenal ulcers in patients between 2006 and 2008 d with no results