The first two authors contributed equally to this work.
IGFBP-2 overexpression reduces the appearance of dysplastic aberrant crypt foci and inhibits growth of adenomas in chemically induced colorectal carcinogenesis
Article first published online: 26 NOV 2008
Copyright © 2009 Wiley-Liss, Inc.
International Journal of Cancer
Volume 124, Issue 9, pages 2220–2225, 1 May 2009
How to Cite
Diehl, D., Hessel, E., Oesterle, D., Renner-Müller, I., Elmlinger, M., Langhammer, M., Göttlicher, M., Wolf, E., Lahm, H. and Hoeflich, A. (2009), IGFBP-2 overexpression reduces the appearance of dysplastic aberrant crypt foci and inhibits growth of adenomas in chemically induced colorectal carcinogenesis. Int. J. Cancer, 124: 2220–2225. doi: 10.1002/ijc.24193
- Issue published online: 24 FEB 2009
- Article first published online: 26 NOV 2008
- Manuscript Accepted: 9 APR 2008
- Manuscript Received: 12 NOV 2007
- German Research Council. Grant Numbers: KFOR128, DFG HO 2003/4-2
- German National Genome Research Network. Grant Numbers: NGFN2, PMM-S31T06
- Hanns Seidel Foundation e.V
- growth inhibition;
- colon cancer;
Colon cancer patients frequently show increased levels of serum insulin-like growth factor-binding protein-2 (IGFBP-2), however, the pathogenetic relevance of this phenomenon for colorectal cancer is unclear. Therefore, we have used IGFBP-2 transgenic animals which overexpress IGFBP-2 systemically and locally in the intestine to study its role in chemically induced colorectal carcinogenesis. Mice received intraperitoneal injections of 1,2-dimethylhydrazine (DMH) (40 mg/kg body weight) once a week for 6 weeks to selectively induce aberrant crypt foci (ACF) and tumors in the colon. While tumor incidence was comparable in transgenic and control mice, the volume of adenomas in IGFBP-2 transgenic mice was reduced more than 2-fold. Furthermore, serum IGFBP-2 levels negatively correlated with tumor volume in the IGFBP-2 transgenic group. Histological examination showed that IGFBP-2 transgenic mice developed significantly less dysplastic ACF with a high potential to progress to advanced stages. The reduced tumor volume in IGFBP-2 transgenic animals was due to significantly reduced proliferative capacity, evidenced by a lower proportion of cells positive for Ki67. Our results demonstrate for the first time in an experimental model that IGFBP-2 overabundance prior to the onset and during colorectal carcinogenesis reduces tumor growth by inhibition of cell proliferation. © 2008 Wiley-Liss, Inc.