Matrix metalloproteinase-9 contributes to intestinal tumourigenesis in the adenomatous polyposis coli multiple intestinal neoplasia mouse

作者: Mark J. Sinnamon , Kathy J. Carter , Barbara Fingleton , Lynn M. Matrisian

DOI: 10.1111/J.1365-2613.2008.00621.X

关键词: ExtracellularProteasesIntestinal mucosaPathologyExtracellular matrixImmunohistochemistryCancer researchMatrix metalloproteinaseAdenomatous polyposis coliApoptosisBiology

摘要: Matrix metalloproteinases (MMPs) are a family of 23 extracellular proteases that best known for their collective ability to degrade all components the matrix. We previously demonstrated genetic ablation MMP-7 reduced tumour multiplicity in multiple intestinal neoplasia (Min) mice possessing alteration adenomatous polyposis coli gene (APC). These mice, commonly referred as APC-Min frequently used model early tumourigenesis. To examine further role MMPs development, we generated genetically deficient MMP-2, -9, -12 or -19. Genetic -19 did not affect size tumours when crossed into system. However, MMP-9 animals developed 40% fewer than littermate controls, although distribution remained unaffected. Intestinal adenomas from 50% decrease proliferating cells compared with control tissues, no difference apoptosis. determine cellular origin these tumours, immunofluorescent co-staining markers different leucocyte lineages was demonstrate intratumoural is largely product neutrophils. studies extend potential targets chemoprevention addition and exclude MMP-2,-12,-19 attractive intervention.

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