Selective inhibition of prostaglandin E2 receptors EP2 and EP4 inhibits invasion of human immortalized endometriotic epithelial and stromal cells through suppression of metalloproteinases

JeHoon Lee, Sakhila K. Banu, Banu SK, Subbarao T, Thenmozhi Subbarao, Anna Starzinski-Powitz, Anna Starzinski‐Powitz, Starzinski-Powitz A, Joe A. Arosh, Arosh JA
Molecular and cellular endocrinology · 2010 · vol. 332(1-2) , pp. 306–313 · doi:10.1016/j.mce.2010.11.022 · PMID:21111772 · W2041847148
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Inhibition of prostaglandin E2 receptors EP2 and EP4 suppresses metalloproteinases, thereby reducing invasion by human immortalized endometriotic epithelial and stromal cells.

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Abstract

Prostaglandin E2 (PGE2) plays an important role in the pathogenesis of endometriosis. We recently reported that inhibition of COX-2 decreased migration as well as invasion of human endometriotic epithelial and stromal cells. Results of the present study indicates that selective inhibition of PGE2 receptors EP2 and EP4 suppresses expression and/or activity of MMP1, MMP2, MMP3, MMP7 and MMP9 proteins and increases expression of TIMP1, TIMP2, TIMP3, and TIMP4 proteins and thereby decreases migration and invasion of human immortalized endometriotic epithelial and stromal cells into matrigel. The interactions between EP2/EP4 and MMPs are mediated through Src and β-arrestin 1 protein complex involving MT1-MMP and EMMPRIN in human endometriotic cells. These novel findings provide an important molecular and cellular framework for further evaluation of selective inhibition of EP2 and EP4 as potential nonsteroidal therapy for endometriosis in childbearing-age women.

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Condition tags

endometriosis

MeSH descriptors

Endometrium Epithelial Cells Matrix Metalloproteinase Inhibitors Receptors, Prostaglandin E, EP2 Subtype Receptors, Prostaglandin E, EP4 Subtype Stromal Cells Cell Movement Cell Movement Cells, Cultured Dinoprostone Dinoprostone Endometriosis Endometriosis Endometriosis Endometrium Epithelial Cells Epithelial Cells Female Humans Receptors, Prostaglandin E, EP2 Subtype

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Cited by (37)

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