title: Role of prostaglandin receptor EP2 in the regulations of cancer cell proliferation, invasion, and inflammation.
abstract: Population studies, preclinical, and clinical trials suggest a role for cyclooxygenase-2 (COX-2, PTGS2) in tumor formation and progression. The downstream prostanoid receptor signaling pathways involved in tumorigenesis are poorly understood, although prostaglandin E2 (PGE(2)), a major COX-2 metabolite which is usually upregulated in the involved tissues, presumably plays important roles in tumor biology. Taking advantage of our recently identified novel selective antagonist for the EP2 (PTGER2) subtype of PGE(2) receptor, we demonstrated that EP2 receptor activation could promote prostate cancer cell growth and invasion in vitro, accompanied by upregulation of the tumor-promoting inflammatory cytokines, such as IL-1β and IL-6. Our results suggest the involvement of prostaglandin receptor EP2 in cancer cell proliferation and invasion possibly via its inflammatory actions, and indicate that selective blockade of the PGE(2)-EP2 signaling pathway via small molecule antagonists might represent a novel therapy for tumorigenesis.
authors.affiliation: Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA. jjiang3@emory.edu
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Jiang
authors.forename: Ray
authors.initials: R
authors.lastname: Dingledine
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D031541:Fluorescence Resonance Energy Transfer; D005910:Glioma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012044:Regression Analysis; D014162:Transfection
chemical_list: D002934:Cinnamates; D016207:Cytokines; D007211:Indoles; C545644:PTGER2 protein, human; D058307:Receptors, Prostaglandin E, EP2 Subtype; C579255:TG4-155