Interstitial cell cyclooxygenase-2 expression is associated with increased angiogenesis in human sporadic colorectal adenomas.
Cyclooxygenase (COX)-2 plays an important role in intestinal tumorigenesis and angiogenesis in animal models. In superficial areas of human sporadic colorectal adenomas, COX-2 is expressed predominantly by interstitial macrophages, in close proximity to microvessels. The aim of this study was to investigate the association between microvessel density (MVD) and COX-2 expression in human sporadic colorectal adenomas. Immunohistochemistry and immunofluorescence for CD31 and COX-2 were performed on a well-characterized series of human sporadic colorectal adenomas (n = 37). The mean MVD and COX-2 expression level (scored 0-3) in superficial and deep interstitial cells of adenomas were assessed by two independent observers. Superficial MVD was increased in COX-2-positive adenomas, compared with COX-2-negative adenomas (p = 0.037). There was a significant correlation between superficial MVD and increasing superficial interstitial cell COX-2 expression score (p = 0.048). COX-2-expressing interstitial cells aggregated in areas of high MVD. No relationship was evident between MVD and COX-2 expression in either deep interstitial cells or epithelial cells. Multivariate analysis demonstrated that only adenoma size (p = 0.005) was a significant independent predictor of MVD. COX-2 protein expression by superficial interstitial cells in human sporadic colorectal adenomas is associated with increased angiogenesis. Promotion of angiogenesis may play a role in the pro-tumourigenic activity of COX-2 during growth of human colorectal adenomas.
Chapple
Keith S
KS
Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK.
Scott
Nigel
N
Guillou
Pierre J
PJ
Coletta
P Louise
PL
Hull
Mark A
MA
D000236:Adenoma / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D000951:Antigens, Neoplasm; D007527:Isoenzymes; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases