Cyclooxygenase 2 is up-regulated and localized to macrophages in the intestine of Min mice.
Expression of cyclooxygenase 2 (COX-2) is believed to play an important role in adenoma formation in murine polyposis models, and inhibition of COX-2 activity may, at least, partly explain the chemopreventative activity of non-steroidal anti-inflammatory drugs against colorectal cancer in humans. However, the mechanism by which COX-2 acts in intestinal tumorigenesis remains unresolved because of conflicting data on the cellular localization of COX-2 in intestinal mucosa. Using immunohistochemistry with specific COX-2 antiserum, we have shown that COX-2 protein is localized to interstitial cells at the base of and within adenomas of the small and large intestine of multiple intestinal neoplasia (Min) mice. No COX-2 staining was observed in dysplastic epithelial cells within adenomas or in histologically normal epithelium. Moreover, COX-2 staining was observed in lamina propria cells of histologically normal intestine of Min mice. No staining was demonstrated in wild-type littermates. The rat monoclonal antibody F4/80 was used to show that COX-2-positive cells represented a subset of the macrophage population present in the intestine of Min mice. Localization of COX-2 to macrophages implies a paracrine effect of COX-2 function on epithelial cells in adenomas and also on histologically normal epithelium. Up-regulation of COX-2 expression in lamina propria macrophages may precede loss of the second functional Apc allele in epithelial cells before adenoma formation in the Min mouse model of intestinal tumorigenesis.
Hull
M A
MA
Molecular Medicine Unit, University of Leeds, UK.
Booth
J K
JK
Tisbury
A
A
Scott
N
N
Bonifer
C
C
Markham
A F
AF
Coletta
P L
PL
D000236:Adenoma / Q000201:enzymology*; D000818:Animals; D003110:Colonic Neoplasms / Q000201:enzymology; D051546:Cyclooxygenase 2; D005260:Female; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology*; D007414:Intestinal Neoplasms / Q000201:enzymology*; D007421:Intestine, Small / Q000166:cytology / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D015854:Up-Regulation
D007527:Isoenzymes; D009363:Neoplasm Proteins; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases