PRESENCE OF IGF-I IN HUMAN MIDGUT CARCINOID-TUMORS - AN AUTOCRINE REGULATOR OF CARCINOID-TUMOR GROWTH

The presence of IGF-I and IGF-I receptors in human midgut carcinoid tumours has been investigated. Using immunocyto-chemistry, IGF-1-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-1. Reverse-phase HPLC of tumour extracts demonstrated a major IGF-1-immunoreactive component eluting in the position of rhlGF-1, 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.