van Adrichem R.C.S. de Herder W.W. K., Kamp M.P., Brugts de Krijger R.R. D.M., Sprij-Mooij S.W.J., Lamberts van Koetsveld P.M. J.A.M.J.L., Janssen L.J., Hofland 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 <b><i>Background:</i></b> 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 D<sub>2</sub> receptors (D2Rs). <b><i>Objectives:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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). <b><i>Conclusions:</i></b> (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. Gastroenteropancreatic neuroendocrine tumors;Insulin-like growth factor 2;Insulin receptor A;Somatostatin analogs;Dopamine agonists;Human pancreatic neuroendocrine tumor cells 2016-02-02
    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
10.6084/m9.figshare.5129545.v1