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The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells.

Journal article
Authors Bo Wängberg
Ola Nilsson
E Theodorsson
A Dahlström
Håkan Ahlman
Published in British journal of cancer
Volume 64
Issue 1
Pages 23-8
ISSN 0007-0920
Publication year 1991
Published at Institute of Laboratory Medicine, Dept of Pathology
Institute of Surgical Sciences, Department of Surgery
Pages 23-8
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Aged, Carcinoid Tumor, metabolism, pathology, secretion, Cells, Cultured, Female, Humans, Hydroxyindoleacetic Acid, urine, Kinetics, Male, Middle Aged, Neoplasm Metastasis, Neuropeptides, secretion, Octreotide, pharmacology, Serotonin, blood, secretion, Tachykinins
Subject categories Surgery

Abstract

The use of a somatostatin analogue (SMS 201-995) has greatly facilitated the treatment of patients with the midgut carcinoid syndrome. Clinical studies have shown that SMS reduces the peripheral levels of tumour-produced serotonin (5-HT) and tachykinins, e.g. neuropeptide K (NPK), basally and after pentagastrin provocation. Some studies have indicated an inhibitory effect of SMS on tumour cell growth as well. In the present study we have investigated the effects of SMS on four different human midgut carcinoid tumours maintained in long term culture. Media levels of 5-HT and NPK-LI in tumour cell cultures decreased rapidly during incubation with SMS (10(-8)-10(-10) M) in all four tumours studied without evidence for tachyphylaxis (up to 6 weeks observation period). SMS treatment (10(-8) M) during 4 days reduced the media concentrations of 5-HT by 56%, while the intracellular contents of 5-HT were decreased by 27% indicating dual inhibitory effects on synthesis and secretion of 5-HT from tumour cells. The DNA contents of cultures were not affected by SMS (10(-8) M or 10(-10) M) treatment for 4 or 14 days. When tumour cell cultures were challenged with isoprenaline (IP) (10(-6) M) no reduction of the IP induced release of 5-HT could be detected after pretreatment of tumour cell cultures with SMS (10(-8) M) for 1 h, 4 h or 4 days. These studies provide evidence for a direct action of the somatostatin analogue on midgut carcinoid tumour cells, reducing both synthesis and secretion of hormones from tumour cells. This effect appears not to be related to inhibition of tumour cell growth. The inhibition of 5-HT secretion from tumour cells by SMS seems to operate via a second messenger system different from the one mediating the beta-adrenoceptor stimulated release of 5-HT.

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