Functional expression of the interleukin-11 receptor alpha-chain in normal colonic epithelium and colon cancer.
BACKGROUND
Interleukin-11 (IL-11) has been evaluated as an anti-inflammatory and mucosa-protective therapeutic agent in inflammatory bowel diseases (IBDs). Activity of IL-11 requires binding to the alpha receptor subunit (IL-11Ralpha) that provides ligand specificity. Recently, we showed that in the intestinal mucosa, IL-11Ralpha is mainly present on epithelial cells mediating antiapoptotic effects. The aim of this study was to investigate the expression profiling of IL-11Ralpha and its downstream signaling cascade in colonic adenoma and carcinoma.


METHODS
The expression of IL-11Ralpha in normal colonic mucosa, 11 colonic adenomas, and 10 carcinomas was analyzed by immunohistochemistry. In addition, IL-11Ralpha-expression and IL-11Ralpha-induced phosphorylation of signal transducer and activator of transcription (STAT)3 were investigated by Western blot analysis.


RESULTS
Immunohistochemistry revealed significant IL-11-Ralpha expression in epithelial cells of normal colonic mucosa. In contrast, the expression of IL-11-Ralpha in colon adenomas and carcinomas was either absent or only detectable in very few scattered epithelial cells. Densitometric analysis of Western blots confirmed these results, showing a decrease of IL-11Ralpha-protein in cells isolated from adenomas or carcinomas. Reduced STAT3-phosphorylation in carcinoma cells indicated functional consequences of decreased IL-11Ralpha-protein expression on signal transduction.


CONCLUSIONS
This study demonstrates a decrease of IL-11-Ralpha-protein expression in epithelial cells isolated from colon carcinomas and adenomas compared to normal colonic mucosa and a reduced STAT3 signaling. Because of reduced binding and signal transduction, it is unlikely that therapeutically administered IL-11 would contribute to colorectal carcinoma induction and growth.
Deutscher
Nicole
N
Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany.
Bataille
Frauke
F
Hausmann
Martin
M
Kiessling
Stephan
S
Muller-Newen
Gerhard
G
Leeb
Sandra N
SN
Herfarth
Hans
H
Heinrich
Peter C
PC
Schölmerich
Jürgen
J
Rogler
Gerhard
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015153:Blotting, Western; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053703:Interleukin-11 Receptor alpha Subunit / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology
D014408:Biomarkers, Tumor; D053703:Interleukin-11 Receptor alpha Subunit