Paracrine cyclooxygenase-2 activity by macrophages drives colorectal adenoma progression in the Apc ^Min/+ mouse model of intestinal tumorigenesis.

ABSTRACT: Genetic deletion or pharmacological inhibition of cyclooxygenase (COX)-2 abrogates intestinal adenoma development at early stages of colorectal carcinogenesis. COX-2 is localised to stromal cells (predominantly macrophages) in human and mouse intestinal adenomas. Therefore, we tested the hypothesis that paracrine Cox-2-mediated signalling from macrophages drives adenoma growth and progression in vivo in the Apc ^Min/+ mouse model of intestinal tumorigenesis. Using a transgenic C57Bl/6 mouse model of Cox-2 over-expression driven by the chicken lysozyme locus (cLys-Cox-2), which directs integration site-independent, copy number-dependent transgene expression restricted to macrophages, we demonstrated that stromal macrophage Cox-2 in colorectal (but not small intestinal) adenomas fr

SUBMITTER: Hull MA 

PROVIDER: S-EPMC5519705 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature