Cyclooxygenase 2- and prostaglandin E2 receptor EP2-dependent angiogenesis in ApcΔ716 mouse intestinal polyps

摘要: To investigate angiogenesis during intestinal polyp development, we determined the microvessel density (MVD) in polyps of Apc knockout ( Δ 716 ) mice, a model for human familial adenomatous polyposis. We scored MVD also several compound mutants carrying , namely, mice with an additional mutation Smad4 which progress into invasive adenocarcinomas; cyclooxygenase (COX)-2 gene Ptgs2 mutation, adenoma growth is suppressed; and prostaglandin E2 EP receptor mutations. In both simple mutants, increased size-dependent manner only expanded beyond threshold about 1 mm diameter. These results indicate that tumor stimulated after tumors grow to certain size, this angiogenic switch common benign adenomas malignant adenocarcinomas. polyposis attenuated by COX-2 contrast, did not increase even larger than mm. The same phenomenon was observed mutant EP2 mutations, but other mutants. immunohistochemically studied factors, vascular endothelial factor basic fibroblast factor. Interestingly, expression these proteins suggest that, mouse tumors, stromal elevated levels stimulate cell surface EP2, followed induction causes angiogenesis.