%0 Generic
%A van Adrichem R.C.S.
%A de Herder W.W.
%A K., Kamp
%A M.P., Brugts
%A de Krijger R.R.
%A D.M., Sprij-Mooij
%A S.W.J., Lamberts
%A van Koetsveld P.M.
%A J.A.M.J.L., Janssen
%A L.J., Hofland
%D 2016
%T Supplementary Material for: Effects of Somatostatin Analogs and Dopamine Agonists on Insulin-Like Growth Factor 2-Induced Insulin Receptor Isoform A Activation by Gastroenteropancreatic Neuroendocrine Tumor Cells
%U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Effects_of_Somatostatin_Analogs_and_Dopamine_Agonists_on_Insulin-Like_Growth_Factor_2-Induced_Insulin_Receptor_Isoform_A_Activation_by_Gastroenteropancreatic_Neuroendocrine_Tumor_Cells/5129545
%R 10.6084/m9.figshare.5129545.v1
%2 https://karger.figshare.com/ndownloader/files/8718085
%K Gastroenteropancreatic neuroendocrine tumors
%K Insulin-like growth factor 2
%K Insulin receptor A
%K Somatostatin analogs
%K Dopamine agonists
%K Human pancreatic neuroendocrine tumor cells
%X Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) express insulin-like growth factor (IGF)-related factors [IGF1, IGF2; insulin receptor (IR)-A, IR-B; IGF-binding protein (IGFBP) 1-3] as well as somatostatin (SSTRs) and dopamine D2 receptors (D2Rs). Objectives: To (1) compare mRNA expression of IGF-related factors in human pancreatic NET (panNET) cell lines with that in human GEP-NETs to evaluate the usefulness of these cells as a model for studying the IGF system in GEP-NETs, (2) determine whether panNET cells produce growth factors that activate IR-A, and (3) investigate whether somatostatin analogs (SSAs) and/or dopamine agonists (DAs) influence the production of these growth factors. Methods: In panNET cells (BON-1 and QGP-1) and GEP-NETs, mRNA expression of IGF-related factors was measured by quantitative real-time PCR. Effects of the SSAs octreotide and pasireotide (PAS), the DA cabergoline (CAB), and the dopastatin BIM-23A760 (all 100 nM) were evaluated at the IGF2 mRNA and protein level (by ELISA) and regarding IR-A bioactivity (by kinase receptor activation assay) in panNET cells. Results: panNET cells and GEP-NETs had comparable expression profiles of IGF-related factors. Especially in BON-1 cells, IGF2 and IR-A were most highly expressed. PAS + CAB inhibited IGF2 (-29.5 ± 4.9%, p < 0.01) and IGFBP3 (-20.0 ± 4.0%, p < 0.01) mRNA expression in BON-1 cells. In BON-1 cells, IGF2 protein secretion was significantly inhibited with BIM-23A760 (-23.7 ± 3.8%). BON-1- but not QGP-1- conditioned medium stimulated IR-A bioactivity. In BON-1 cells, IR-A bioactivity was inhibited by BIM-23A760 and PAS + CAB (-37.8 ± 2.1% and -30.9 ± 4.1%, respectively, p < 0.0001). Conclusions: (1) The BON-1 cell line is a representative model for studying the IGF system in GEP-NETs, (2) BON-1 cells produce growth factors (IGF2) activating IR-A, and (3) combined SSTR and D2R targeting with PAS + CAB and BIM-23A760 suppresses IGF2-induced IR-A activation.
%I Karger Publishers