Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth?
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 rhIGF-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.
Nilsson
O
O
Department of Histology, University of Göteborg, Sweden.
Wängberg
B
B
Theodorsson
E
E
Skottner
A
A
Ahlman
H
H
D000328:Adult; D000368:Aged; D002276:Carcinoid Tumor / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis; D005260:Female; D006801:Humans; D007078:Ileal Neoplasms / Q000737:chemistry* / Q000378:metabolism; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics; D017451:Receptors, Somatomedin
D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D004247:DNA