Increasing evidence indicates that Prostaglandin E2 (PGE2) promotes lung tumor growthby stimulating prostaglandin E receptor type 4 (EP4) signalling with subsequentenhancement of cellular proliferation, metastasis and suppression of immune responses.However, the role of other EP receptors in cancer is still not known. We hypothesized thatprostanoid receptors other than the EP4 receptor might be involved in progression of Lungcancer.We analyzed the expression profile of EP receptors in lung adenocarcinoma cell lines A549and H1299 by using RT-PCR, western blotting and immunofluorescence. All four EPreceptors were found to be expressed in both cell lines. While EP1 and EP2 receptors werelocalized on both cell and nuclear membrane, expression of EP3 and EP4 receptors waslimited to the cell membrane.The EP4 receptor antagonist, L-161982 and the EP1 receptor antagonist SC-51322inhibited proliferation of both NSCLC cell lines. EP2 and EP3 receptor blockers did notinhibit proliferation. SC-51322 did not show any effect on cAMP levels in A549.Interestingly, it led to a decrease in intracellular calcium levels suggesting a contribution ofcalcium signaling to proliferation of cancer cells.The anti-proliferative effects of EP1 receptor inhibition was proved to be largely due to adecrease in intracellular calcium levels that may subsequently alter downstream signalingevents such as phosphorylation of the Extra cellular Regulated Kinase (ERK). In ourinvestigation, we found that inhibition of EP1 receptor by employing the selective inhibitorSC-51322, did not elicit an increase in intracellular calcium, reduced ERK phosphorylationand attenuated proliferation of A549 and H1299 cells. Furthermore, SC-51322 inhibitedmigration of A549 cells in presence of FCS and the EP1 receptor specific agonist 17-P-T-PGE2.Taken together, this study supports a central role of EP1 receptor in progression andmigration of A549 cells. Investigating the signaling pathway downstream to EP1 receptorwill provide us with a better understanding of the contribution of this pathway in lung cancerand a novel therapeutic opportunity for the treatment of NSCLC.
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