Functional expression of the interleukin-11 receptor alpha-chain in normal colonic epithelium and colon cancer

• Published in: International journal of colorectal disease 2006-09, Vol.21 (6), p.573-581
• Main Authors: DEUTSCHER, Nicole, BATAILLE, Frauke, HAUSMANN, Martin, KIESSLING, Stephan, MULLER-NEWEN, Gerhard, LEEB, Sandra N, HERFARTH, Hans, HEINRICH, Peter C, SCHÖLMERICH, Jürgen, ROGLER, Gerhard
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Blotting, Western; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Disease Progression; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry; Interleukin-11 Receptor alpha Subunit - biosynthesis; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Male; Medical sciences; Middle Aged; Signal Transduction - physiology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0179-1958; 1432-1262
• DOI: 10.1007/s00384-005-0055-8

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. 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. 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. 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.