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 (PGE2), 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 PGE2 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 PGE2-EP2 signaling pathway via small molecule antagonists might represent a novel therapy for tumorigenesis.
Footnotes
This work was supported by the Epilepsy Foundation (to J.J.); the CounterACT Program, National Institutes of Health Office of the Director; the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant U01NS058158] (to R.D.); and the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant R21NS074169] (to R.D.).
National Institutes of Health Office of the Director (OD) and the National Institute of Neurologic Disorders and Stroke (NINDS), Grant Number [U01NS058158]; and National Institute of Neurologic Disorders and Stroke (NINDS), Grant Number [R21NS074169].
- Received September 19, 2012.
- Accepted November 26, 2012.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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