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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

3-Iodobenzylguanidine

pharmacokinetics

5-Hydroxytryptophan

secretion

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

diagnostic use

pharmacokinetics

Receptors

Somatostatin

genetics

metabolism

Serotonin

analysis

secretion

Substance P

analysis

Transplantation

Heterologous

Tumor Cells

Cultured

metabolism

Vesicular Biogenic Amine Transport Proteins

Vesicular Monoamine Transport Proteins

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