COLORECTAL CANCER

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

J Thulesen¹, B Hartmann², K J Hare², H Kissow², C Ørskov¹, J J Holst², S S Poulsen¹

¹ Department of Medical Anatomy, Section B, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
² Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

Correspondence to:
Correspondence to:
Dr J Thulesen
Naestved Hospital, Department 18, Ringstedgade 61, 4700 Naestved, Denmark; J.Thulesen{at}dadlnet.dk

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.

Abbreviations: GLP-2, glucagon-like peptide 2; DMH, 1,2-dimethylhydrazine; PBS, phosphate buffered saline

Keywords: intestinal carcinogenesis; 1,2-dimethylhydrazine; glucagon-like peptide 2; mice

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