TITLE

EXPRESSION OF MACROPHAGE MIGRATION INHIBITORY FACTOR IN INTESTINAL ADENOMAS

AUTHOR(S)
Wilson, J.M.; Scott, N.; Guillou, P.J.; Markham, A.F.; Coletta, P.L.; Hull, M.A.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA30
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: The cytokine macrophage migration inhibitory factor (MIF) is expressed in normal human colorectal mucosa and promotes tumour growth in several experimental cancer models. Aims: The aim of this study was to investigate MIF expression and activity in human sporadic colorectal adenomas and in intestinal adenomas from the Apc[sup Min/+] mouse model of familial adenomatous polyposis. Methods: Immunohistochemistry was performed on archival formalin-fixed, paraffin-embedded human sporadic colorectal adenomas (n = 56), and on small and large intestine of Apc[sup Min/+] mice and wild-type littermates. Human MIF protein levels were analysed in fresh paired colorectal adenoma and normal mucosal samples by ELISA (n = 16) and by Western blot analysis (n = 8). A p-hydroxyphenylpyruvate (HPP) tautomerase assay was used to measure specific MIF activity in paired fresh tissue (n = 20). Results: In human colorectal tissue, immunohistochemistry and Western blot analysis both demonstrated increased MIF protein levels in adenomas compared with paired normal colorectal mucosa. MIF was Iocalised to both epithelial (particularly at the apical membrane) and stromal cells in adenomas. The ELISA demonstrated a mean 1.9fold increase (95% C] 1.1 to 2.7) in immunoreactive MIF in adenomas compared with paired normal mucosa. The HPP tautomerase assay revealed a mean 1.5-fold increase (95% CI 1.2 to 1.7) in MIF activity in adenomas. Immunohistochemical analysis of Apc[sup Min/+] mouse intestine revealed a similar pattern of protein Iocalisation in adenomas and histologically normal mucosa, with prominent MIF protein expression by dysplastic epithelial cells in adenomas. Conclusions: MIF protein levels are increased in human sporadic colorectal adenomas and in intestinal adenomas from the Apc[sup Min/+] mouse. The precise role of MIF in epithelial and stromal cell compartments of adenomas during the early stages of intestinal tumorigenesis is currently being investigated.
ACCESSION #
9747461

 

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