Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps.
Cyclooxygenase-2 (COX-2), the inducible COX isozyme, plays a key role in intestinal tumorigenesis. We have demonstrated recently that COX-2 protein is induced in the polyp stroma near the intestinal luminal surface in the Apc(Delta716) mouse, a model for human familial adenomatous polyposis, and stimulate tumor angiogenesis. However, the precise cell types that express COX-2 are still to be determined. By immunohistochemical analysis, here we show that the majority of COX-2-expressing cells in the intestinal polyps of Apc(Delta716) mice are fibroblasts and endothelial cells. Furthermore, the COX-2-expressing cells in human familial adenomatous polyposis polyps are also fibroblasts and endothelial cells. In contrast, bone marrow-derived cells such as macrophages and leukocytes express little COX-2 protein in the intestinal polyps. These results clearly indicate that fibroblasts and endothelial cells play important roles in polyp expansion by expressing COX-2, resulting in tumor angiogenesis.
Sonoshita
Masahiro
M
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Takaku
Kazuaki
K
Oshima
Masanobu
M
Sugihara
Ken-ichi
K
Taketo
Makoto M
MM
D000199:Actins / Q000096:biosynthesis; D011125:Adenomatous Polyposis Coli / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007417:Intestinal Polyps / Q000201:enzymology* / Q000473:pathology; D007527:Isoenzymes / Q000096:biosynthesis*; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D017154:Stromal Cells / Q000201:enzymology / Q000378:metabolism; D014746:Vimentin / Q000096:biosynthesis
D000199:Actins; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D007527:Isoenzymes; D008565:Membrane Proteins; D014746:Vimentin; C036763:monocyte-macrophage differentiation antigen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases