Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice

• Published in: Gut Vol. 53; no. 8; pp. 1145 - 1150
• Main Authors: Thulesen, J, Hartmann, B, Hare, K J, Kissow, H, Ørskov, C, Holst, J J, Poulsen, S S
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.08.2004; BMJ; BMJ Publishing Group LTD; Copyright 2004 by Gut
• Subjects: 2-dimethylhydrazine; Adenoma - pathology; Adenoma - physiopathology; Animals; Biological and medical sciences; Body Weight; Cancer; Carcinogens; Colon; Colonic Neoplasms - chemically induced; Colonic Neoplasms - pathology; Colonic Polyps - chemically induced; Colonic Polyps - pathology; Colorectal Cancer; DMH; Female; Gastroenterology. Liver. Pancreas. Abdomen; GLP-2; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Inflammatory bowel disease; intestinal carcinogenesis; Intestinal Mucosa - pathology; Intestine, Small - pathology; Medical sciences; Metabolism; Mice; Mice, Inbred C57BL; Organ Size; PBS; Peptides; Peptides - adverse effects; phosphate buffered saline; Rodents; Studies; Tumors; Vertebrata; Mammalia; Glucagon; Peptides; Mouse; Growth; Animal; Rodentia; Gastroenterology; Colon; Malignant tumor
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.2003.035212

Background: Glucagon-like peptide 2 (GLP-2) is an intestinotrophic mediator with therapeutic potential in conditions with compromised intestinal capacity. However, growth stimulation of the intestinal system may accelerate the growth of existing neoplasms in the intestine. Aims: In the present study, the effects of GLP-2 treatment on the growth of chemically induced colonic neoplasms were investigated. Methods: In 210 female C57bl mice, colonic tumours were initially induced with the methylating carcinogen 1,2-dimethylhydrazine (DMH) and mice were then treated with GLP-2. Two months after discontinuation of the carcinogen treatment, 135 of the mice were allocated to one of six groups which were treated twice daily with 25 μg GLP-2, 25 μg Gly2-GLP-2 (stable analogue), or phosphate buffered saline for a short (10 days) or long (one month) period. The remaining 75 mice had a treatment free period of three months and were then allocated to groups subjected to long term treatment, as above. Results: Colonic polyps developed in 100% of the mice, regardless of treatment. Survival data revealed no statistical significant differences among the different groups but histopathological analysis demonstrated a clear and significant increase in tumour load of mice treated with Gly2-GLP-2. The tumour promoting effect of native GLP-2 was less pronounced but the number of small sized polyps increased following long term treatment. Conclusions: The present results clearly indicate that GLP-2 promotes the growth of mucosal neoplasms. Our findings highlight the need for future investigations on the effects of GLP-2 in conditions needing long time treatment or with increased gastrointestinal cancer susceptibility.