BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from human colorectal adenoma epithelium might be involved in COX-2 expression in macrophages of the lamina propria. METHODS: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenoma macrophage chemoattractant protein 1 (MCP-1) and COX-2 were determined by immunohistochemistry. The effects of MCP-1, in the presence or absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E(2) and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood. RESULTS: MCP-1 levels were markedly higher in adenoma with mild-moderate dysplasia (129.7 (19.9) pg/mg protein) and severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8 (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)-1alpha and MIP-1beta, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP-1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP-1 stimulated COX-2 expression and PGE(2) and VEGF release in human macrophages. Celecoxib, a selective COX-2 inhibitor, inhibited MCP-1-induced PGE(2) and VEGF release in macrophages. Addition of exogenous PGE(2) reversed this inhibitory effect on VEGF release, suggesting that MCP-1 in adenoma epithelial cells might be involved in COX-2 expression and subsequent macrophage activation. CONCLUSIONS: MCP-1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX-2 expression, leading to the subsequent development of colonic adenoma.
BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from humancolorectal adenoma epithelium might be involved in COX-2 expression in macrophages of the lamina propria. METHODS: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenomamacrophage chemoattractant protein 1 (MCP-1) and COX-2 were determined by immunohistochemistry. The effects of MCP-1, in the presence or absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E(2) and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood. RESULTS:MCP-1 levels were markedly higher in adenoma with mild-moderate dysplasia (129.7 (19.9) pg/mg protein) and severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8 (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)-1alpha and MIP-1beta, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP-1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP-1 stimulated COX-2 expression and PGE(2) and VEGF release in human macrophages. Celecoxib, a selective COX-2 inhibitor, inhibited MCP-1-induced PGE(2) and VEGF release in macrophages. Addition of exogenous PGE(2) reversed this inhibitory effect on VEGF release, suggesting that MCP-1 in adenoma epithelial cells might be involved in COX-2 expression and subsequent macrophage activation. CONCLUSIONS:MCP-1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX-2 expression, leading to the subsequent development of colonic adenoma.
Authors: H Tabara; H Kohno; D K Dhar; T Kotoh; H Yoshimura; R Masunaga; M Tachibana; H Kubota; N Nagasue Journal: Acta Oncol Date: 2001 Impact factor: 4.089
Authors: G Steinbach; P M Lynch; R K Phillips; M H Wallace; E Hawk; G B Gordon; N Wakabayashi; B Saunders; Y Shen; T Fujimura; L K Su; B Levin; L Godio; S Patterson; M A Rodriguez-Bigas; S L Jester; K L King; M Schumacher; J Abbruzzese; R N DuBois; W N Hittelman; S Zimmerman; J W Sherman; G Kelloff Journal: N Engl J Med Date: 2000-06-29 Impact factor: 91.245
Authors: Carl N Sprung; Alesia Ivashkevich; Helen B Forrester; Christophe E Redon; Alexandros Georgakilas; Olga A Martin Journal: Cancer Lett Date: 2013-09-14 Impact factor: 8.679
Authors: Songbai Lin; Dongsheng Wang; Smita Iyer; Amr M Ghaleb; Hyunsuk Shim; Vincent W Yang; Jerold Chun; C Chris Yun Journal: Gastroenterology Date: 2009-01-09 Impact factor: 22.682