Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 31, 2015, Pages 9716-9721

  Arosh, Joe A ^a   Lee, JeHoon ^a   Balasubbramanian, Dakshnapriya ^a   Stanley, Jone A ^a   Long, Charles R ^b   Meagher, Mary W ^a   Osteen, Kevin G ^c   Bruner Tran, Kaylon L ^c   Burghardt, Robert C ^a   Starzinski Powitz, Anna ^d   Banu, Sakhila K ^a  

^a TEXAS A AND M UNIVERSITY   (United States)

^b TEXAS A AND M UNIVERSITY   (United States)

^c VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d GOETHE UNIVERSITY   (Germany)

Author keywords

Endometriosis; Infertility; Pain pathways; Pelvic pain; PGE2 signaling

Indexed keywords

NONSTEROID ANTIINFLAMMATORY AGENT; PROSTAGLANDIN E RECEPTOR 2; PROSTAGLANDIN E RECEPTOR 4; 6-ISOPROPOXY-9-OXOXANTHENE-2-CARBOXYLIC ACID; 7 [5 (4 BIPHENYLYLMETHOXY) 2 MORPHOLINO 3 OXOCYCLOPENTYL] 4 HEPTENOIC ACID; BIPHENYL DERIVATIVE; CASPASE 3; ESTROGEN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PROGESTERONE; STEROID; XANTHONE DERIVATIVE;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENDOMETRIOSIS; FEMALE; INNERVATION; MOUSE; NONHUMAN; PELVIC PAIN; PERITONEAL FLUID; PRIORITY JOURNAL; SPINAL GANGLION; ANIMAL; ANTAGONISTS AND INHIBITORS; APOPTOSIS; BIOSYNTHESIS; CELL LINE; CELL MOTION; CELL SURVIVAL; DISEASE MODEL; DRUG EFFECTS; ENDOMETRIUM; HUMAN; INFLAMMATION; METABOLISM; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY; SIGNAL TRANSDUCTION; VASCULARIZATION;

ANIMALS; APOPTOSIS; BIPHENYL COMPOUNDS; CASPASE 3; CELL LINE; CELL MOVEMENT; CELL SURVIVAL; DISEASE MODELS, ANIMAL; ENDOMETRIOSIS; ENDOMETRIUM; ESTROGENS; FEMALE; HUMANS; INFLAMMATION; MICE; NEOVASCULARIZATION, PATHOLOGIC; PELVIC PAIN; POLY(ADP-RIBOSE) POLYMERASES; PROGESTERONE; RECEPTORS, PROSTAGLANDIN E, EP2 SUBTYPE; RECEPTORS, PROSTAGLANDIN E, EP4 SUBTYPE; SIGNAL TRANSDUCTION; STEROIDS; XANTHONES;

EID: 84938650884     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1507931112     Document Type: Article

References (37)

1. Bulun SE (2009) Endometriosis. N Engl J Med 360(3):268-279.
2. Giudice LC, Kao LC (2004) Endometriosis. Lancet 364(9447):1789-1799.
3. Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of endometriosis. Fertil Steril 98(3):511-519.
4. Sampson J (1927) Peritoneal endometritis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14:442-469.
5. Guo SW, Olive DL (2007) Two unsuccessful clinical trials on endometriosis and a few lessons learned. Gynecol Obstet Invest 64(1):24-35.
6. Wu MH, Lu CW, Chuang PC, Tsai SJ (2010) Prostaglandin E2: The master of endometriosis? Exp Biol Med (Maywood) 235(6):668-677.
7. Cobellis L, et al. (2004) The treatment with a COX-2 specific inhibitor is effective in the management of pain related to endometriosis. Eur J Obstet Gynecol Reprod Biol 116(1):100-102.
8. Laschke MW, Elitzsch A, Scheuer C, Vollmar B, Menger MD (2007) Selective cyclooxygenase-2 inhibition induces regression of autologous endometrial grafts by down-regulation of vascular endothelial growth factor-mediated angiogenesis and stimulation of caspase-3-dependent apoptosis. Fertil Steril 87(1):163-171.
9. Olivares C, et al. (2008) Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis. Hum Reprod 23(12):2701-2708.
10. Narumiya S, Sugimoto Y, Ushikubi F (1999) Prostanoid receptors: Structures, properties, and functions. Physiol Rev 79(4):1193-1226.
11. Banu SK, Lee J, Speights VO, Jr, Starzinski-Powitz A, Arosh JA (2009) Selective inhibition of prostaglandin E2 receptors EP2 and EP4 induces apoptosis of human endometriotic cells through suppression of ERK1/2, AKT, NFkappaB, and beta-catenin pathways and activation of intrinsic apoptotic mechanisms. Mol Endocrinol 23(8): 1291-1305.
12. Lee J, Banu SK, Burghardt RC, Starzinski-Powitz A, Arosh JA (2013) Selective inhibition of prostaglandin E2 receptors EP2 and EP4 inhibits adhesion of human endometriotic epithelial and stromal cells through suppression of integrin-mediated mechanisms. Biol Reprod 88(3):77.
13. Lee J, Banu SK, Rodriguez R, Starzinski-Powitz A, Arosh JA (2010) Selective blockade of prostaglandin E2 receptors EP2 and EP4 signaling inhibits proliferation of human endometriotic epithelial cells and stromal cells through distinct cell cycle arrest. Fertil Steril 93(8):2498-2506.
14. Lee J, Banu SK, Subbarao T, Starzinski-Powitz A, Arosh JA (2011) Selective inhibition of prostaglandin E2 receptors EP2 and EP4 inhibits invasion of human immortalized endometriotic epithelial and stromal cells through suppression of metalloproteinases. Mol Cell Endocrinol 332(1-2):306-313.
15. Osteen KG, Igarashi TM, Yeaman GR, Bruner-Tran KL (2004) Steroid and cytokine regulation of matrix metalloproteinases and the pathophysiology of endometriosis. Gynecol Obstet Invest 57(1):53-54.
16. Bulun SE, et al. (2010) Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis. Semin Reprod Med 28(1):36-43.
17. Bruner-Tran KL, Herington JL, Duleba AJ, Taylor HS, Osteen KG (2013) Medical management of endometriosis: Emerging evidence linking inflammation to disease pathophysiology. Minerva Ginecol 65(2):199-213.
18. De Leon FD, et al. (1986) Peritoneal fluid volume, estrogen, progesterone, prostaglandin, and epidermal growth factor concentrations in patients with and without endometriosis. Obstet Gynecol 68(2):189-194.
19. Gazvani R, Templeton A (2002) Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction 123(2):217-226.
20. Lin CR, et al. (2006) Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity. J Pharmacol Exp Ther 319(3):1096-1103.
21. Samad TA, Sapirstein A, Woolf CJ (2002) Prostanoids and pain: Unraveling mechanisms and revealing therapeutic targets. Trends Mol Med 8(8):390-396.
22. Vardeh D, et al. (2009) COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice. J Clin Invest 119(2):287-294.
23. Amaya F, Samad TA, Barrett L, Broom DC, Woolf CJ (2009) Periganglionic inflammation elicits a distally radiating pain hypersensitivity by promoting COX-2 induction in the dorsal root ganglion. Pain 142(1-2):59-67.
24. Berkley KJ, Dmitrieva N, Curtis KS, Papka RE (2004) Innervation of ectopic endometrium in a rat model of endometriosis. Proc Natl Acad Sci USA 101(30):11094-11098.
25. Stratton P, Khachikyan I, Sinaii N, Ortiz R, Shah J (2015) Association of chronic pelvic pain and endometriosis with signs of sensitization and myofascial pain. Obstet Gynecol 125(3):719-728.
26. Al-Sabbagh M, Lam EW, Brosens JJ (2012) Mechanisms of endometrial progesterone resistance. Mol Cell Endocrinol 358(2):208-215.
27. Lessey BA, Lebovic DI, Taylor RN (2013) Eutopic endometrium in women with endometriosis: Ground zero for the study of implantation defects. Semin Reprod Med 31(2):109-124.
28. Fazleabas AT (2010) Progesterone resistance in a baboon model of endometriosis. Semin Reprod Med 28(1):75-80.
29. Zeitvogel A, Baumann R, Starzinski-Powitz A (2001) Identification of an invasive, N-cadherin-expressing epithelial cell type in endometriosis using a new cell culture model. Am J Pathol 159(5):1839-1852.
30. Banu SK, Starzinski-Powitz A, Speights VO, Burghardt RC, Arosh JA (2009) Induction of peritoneal endometriosis in nude mice with use of human immortalized endometriosis epithelial and stromal cells: A potential experimental tool to study molecular pathogenesis of endometriosis in humans. Fertil Steril 91(5, Suppl):2199-2209.
31. Golding MC, Zhang L, Mann MR (2010) Multiple epigenetic modifiers induce aggressive viral extinction in extraembryonic endoderm stem cells. Cell Stem Cell 6(5): 457-467.
32. Miyoshi H, Blömer U, Takahashi M, Gage FH, Verma IM (1998) Development of a self-inactivating lentivirus vector. J Virol 72(10):8150-8157.
33. Byers SL, Wiles MV, Dunn SL, Taft RA (2012) Mouse estrous cycle identification tool and images. PLoS One 7(4):e35538.
34. Bruner-Tran KL, et al. (2002) Steroid and cytokine regulation of matrix metalloproteinase expression in endometriosis and the establishment of experimental endometriosis in nude mice. J Clin Endocrinol Metab 87(10):4782-4791.
35. Malin SA, Davis BM, Molliver DC (2007) Production of dissociated sensory neuron cultures and considerations for their use in studying neuronal function and plasticity. Nat Protoc 2(1):152-160.
36. Lee J, Banu SK, Nithy TK, Stanley JA, Arosh JA (2012) Early pregnancy induced expression of prostaglandin E2 receptors EP2 and EP4 in the ovine endometrium and regulated by interferon tau through multiple cell signaling pathways. Mol Cell Endocrinol 348(1):211-223.
37. Caceres G, et al. (2003) Imaging of luciferase and GFP-transfected human tumours in nude mice. Luminescence 18(4):218-223.