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Presence of IGF‐I In human midgut carcinoid tumours—an autocrine regulator of carcinoid tumour growth?
Author(s) -
Nilsson Ola,
Wängberg Bo,
Theodorsson Elvar,
Skottner Anna,
Ahlman Håkan
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910510206
Subject(s) - autocrine signalling , paracrine signalling , biology , immunocytochemistry , receptor , somatostatin , carcinoid tumour , endocrinology , medicine , chromogranin a , immunohistochemistry , immunology , biochemistry
The presence of IGF‐I and IGF‐I receptors in human midgut carcinoid tumours has been investigated. Using immunocytochemistry, IGF‐I‐positive tumour cells were demonstrated in 11/11 tumour cases studied. Labelling of consecutive sections with antibodies against IGF‐I and proliferating cell nuclear antigen (PCNA)/cyclin demonstrated a co‐distribution of the 2 antigens in carcinoid tumours. Extracts of tumour tissues were subjected to radioimmunoassay and shown to contain significant amounts of IGF‐I. Reverse‐phase HPLC of tumour extracts demonstrated a major IGF‐I‐immunoreactive component eluting in the position of rhlGF‐I, but also 2 other more hydrophobic forms. Conditioned serum‐free media from primary cultures of carcinoid tumors contained detectable amounts of IGF‐I, indicating a spontaneous release of IGF‐I from tumour cells into the culture medium. Levels of IGF‐I in media were reduced (19%) after incubation of cultures with a somatostatin analogue for 4 days. IGF‐I receptors were observed on tumour cells in 4/10 tumours by immunocytochemistry. Tumour cells with immunoreactive IGF‐I receptors could be stimulated to enhanced growth, measured as an increase in DNA contents, by exogenous administration of IGF‐I every 3–4 days for 2 weeks. The results show that cultured human midgut carcinoid tumours secrete IGF‐I and that some of the tumours also have IGF‐I receptors. We therefore suggest that IGF‐I may act as an autocrine or paracrine regulator of carcinoid tumour‐cell growth.