Mucosal prostanoid receptors and synthesis in familial adenomatous polyposis

Chronic ingestion of non-steroidal antiinflammatory medication is reported to delay or, in part, reverse development of polyps in the colon, but the m echanism for this effect is unknown. Using mRNA and immunoglobulin probes, specific for prostanoid receptors and for prostaglandin endoperoxide syntha se (COX 1 and 2), we sought to define, by in situ and in vitro techniques, changes in PGE(2) receptors and synthesis in cell populations of precancero us familial adenomatous polyposis (FAP) colonic mucosa. In FAP, expression of prostanoid receptors EP3 and EP4 among colonic lamina propria mononuclea r and lateral crypt epithelial cells was robust, with 53.9 +/-5.3% of monon uclear cells staining EP4+. When sections of normal colonic mucosa were exa mined by similar techniques, prostanoid receptor EP4 was expressed on only 21.3 +/-0.2% of lamina propria mononuclear cells (including CD4(+) T lympho cytes), as well as on surface and lateral crypt epithelium, and this distri bution was found at the mRNA level as well. When receptor expression was qu antitated by densitometry, immunoreactive EP3 protein on deep basolateral ( but not other) FAP crypt epithelium was enhanced 2.8-fold over normal, and the number of prostanoid receptor EP4+ mononuclear cells by 2.5-fold. On th e other hand, while COX 1 expression in mononuclear cells was prominent in normal and FAP mucosa, densitometric analysis showed immunoreactive prostag landin endoperoxide synthase levels were further increased in FAP, due to a greater than fourfold elevation of COX 2 expression among mononuclear cell s and epithelia. Our data suggest enhanced cell-specific prostanoid recepto r expression and increased prostanoid synthesis in precancerous FAP mucosa.