A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake.

Abstract	A human midgut carcinoid tumor was successfully transplanted into nude mice and propagated for five consecutive generations (30 months) with well-preserved phenotype. Tumor cells in nude mice expressed identical neuroendocrine markers as the original tumor, including somatostatin receptors (somatostatin receptors 1 to 5) and vesicular monoamine transporters (VMAT1 and VMAT2). Because of the expression of somatostatin receptors and VMAT1 and VMAT2 the grafted tumors could be visualized scintigraphically using the somatostatin analogue 111In-octreotide and the catecholamine analogue 123I-metaiodobenzylguanidine. The biokinetics of the somatostatin analogue 111In-octreotide in the tumors was studied and showed a high retention 7 days after administration. Cell cultures were re-established from transplanted tumors. Immunocytochemical and ultrastructural studies confirmed the neuroendocrine differentiation. The human origin of transplanted tumor cells was confirmed by cytogenetic and fluorescence it situ hybridization analyses. Spontaneous secretion of serotonin and its metabolite, 5-hydroxyindole acetic acid, from tumor cells was demonstrated. The tumor cells increased their [Ca2+]i in response to beta-adrenoceptor stimulation (isoproterenol) and K+-depolarization. All somatostatin receptor subtypes could be demonstrated in cultured cells. This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatostatin receptor- and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms.
Authors	L Kölby, P Bernhardt, H Ahlman, B Wängberg, V Johanson, A Wigander, E Forssell-Aronsson, S Karlsson, B Ahrén, G Stenman, O Nilsson
Journal	The American journal of pathology (Am J Pathol) Vol. 158 Issue 2 Pg. 745-55 (Feb 2001) ISSN: 0002-9440 [Print] United States
PMID	11159212 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Biogenic Amines Carrier Proteins Chromogranin A Chromogranins Membrane Glycoproteins Membrane Transport Proteins Neuropeptides RNA, Messenger Radioisotopes Receptors, Somatostatin SLC18A1 protein, human SLC18A2 protein, human Slc18a1 protein, mouse Slc18a2 protein, mouse Vesicular Biogenic Amine Transport Proteins Vesicular Monoamine Transport Proteins Serotonin Substance P 3-Iodobenzylguanidine Hydroxyindoleacetic Acid 5-Hydroxytryptophan Octreotide Calcium
Topics	3-Iodobenzylguanidine (pharmacokinetics) 5-Hydroxytryptophan (metabolism) Animals Biogenic Amines (metabolism) Calcium (metabolism) Carcinoid Tumor (metabolism, pathology) Carrier Proteins (metabolism) Chromogranin A Chromogranins (analysis) Chromosome Painting Disease Models, Animal Female Gene Expression Regulation, Neoplastic Humans Hydroxyindoleacetic Acid (metabolism) Ileal Neoplasms (metabolism, pathology) Immunohistochemistry Male Membrane Glycoproteins (analysis) Membrane Transport Proteins Mice Mice, Nude Middle Aged Neuropeptides Octreotide (pharmacokinetics) RNA, Messenger (genetics, metabolism) Radioisotopes (pharmacokinetics) Receptors, Somatostatin (genetics, metabolism) Serotonin (analysis, metabolism) Substance P (analysis) Transplantation, Heterologous Tumor Cells, Cultured (metabolism) Vesicular Biogenic Amine Transport Proteins Vesicular Monoamine Transport Proteins

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