Targeting Prostaglandin E EP Receptors to Inhibit Metastasis

Cancer Res. 2006 Oct 15;66(20):9794-7. doi: 10.1158/0008-5472.CAN-06-2067.

Abstract

It is well established that high cyclooxygenase-2 (COX-2) expression contributes to the aggressive behavior of breast and other malignancies. Due to concerns regarding the safety of long-term use of COX-2 inhibitors as well as a desire to seek more effective alternatives to prevent and treat metastatic disease, we tested the hypothesis that inhibition of downstream signaling by the COX-2 product prostaglandin E(2) (PGE(2)) would be as effective as inhibiting global prostaglandin synthesis. PGE(2) acts through four G-protein-coupled receptors designated EP1-4. Here, we summarize data from many laboratories regarding the role of individual E-series of prostaglandin (EP) receptors on cancer behavior and we discuss our own recent findings that antagonists of the PGE receptor subtype 4, EP4, inhibit experimental metastasis in a murine model of hormone-resistant, metastatic breast cancer. These initial results indicate that selective targeting of individual EP receptors should be investigated as an approach to exploit the high COX-2 activity in many epithelial malignancies.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cyclooxygenase 2 / metabolism
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Receptors, Prostaglandin E / antagonists & inhibitors*
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E / physiology
  • Receptors, Prostaglandin E, EP4 Subtype

Substances

  • PTGER4 protein, human
  • Ptger4 protein, mouse
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP4 Subtype
  • Cyclooxygenase 2