Endocrine Abstracts

Objectives: The Wnt-signalling pathway is involved in tumor development in various tissues. Wnt-signalling molecules are expressed in pancreatic beta-cells. In addition, Wnt-signalling regulates insulin secretion and the proliferation of pancreatic beta-cells in vitro and in animal models. However, it is not clear whether Wnts play a role for the development of human insulinomas. Therefore, we investigated the expression pattern of Wnt-signalling molecules in benign and malign human insulinomas.

Methods: human insulinomas were analysed using tissues arrays. The insulinomas were classified as benign (n=49) or malign (n=10). Immunohistochemistry (IHC) for Wnt3a, Wnt4 and frizzled was performed. The expression of these molecules was assessed with a score model (expression level multiplied by number of positive cells, maximum score: 12). Healthy pancreas sections served as controls. Proliferation assays ([3H]-thymidine uptake) of INS-1 insulinoma cells were performed after stimulation with Wnt3a protein.

Results: 1 Wnt3a, Wnt4 and frizzled are expressed in the normal human endocrine pancreas (control group). 2. The extracellular ligand Wnt3a is strongly over-expressed in human insulinomas (benign: 7.59±3.20, P<0.05; malign: 3.39±2.51, n.s.) compared to controls (2.50±0.50). 3. The Wnt-receptor frizzled is over-expressed in insulinomas (benign: 6.21±3.44, P<0.05; malign: 5.47±3.34, P<0.05) compared to healthy control pancreas (1.5±0.50). Using in vitro assays we found Wnt3a to induce the proliferation of INS-1 insulinoma cells to 151.2% of untreated controls.

Conclusions: These data demonstrate that the expression of Wnt3a and frizzled is increased in human insulinomas compared to normal endocrine pancreatic tissue. On the functional level, Wnt3a stimulates the proliferation of insulinoma cells in vitro. This suggests that dysregulated Wnt-signalling is involved in the development of insulinomas. Wnt-signalling molecules are not useful as markers for malignancy.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.