GROWTH-FACTORS AND CARCINOID-TUMORS

The presence of growth factors and their receptors in human midgut car cinoids and in gastric carcinoids of Mastomys have been investigated. Human midgut carcinoid tumours produce IGF-I as demonstrated by immuno cytochemistry and radioimmunoassay. IGF-I receptors were detectable in half of the tumours and stimulation of cultured tumour cells with IGF -I enhanced DNA synthesis. IGF-I may therefore act as an autocrine sti mulator of carcinoid tumour growth. Expression of TGF-alpha and EGF-re ceptors could also be demonstrated in midgut carcinoids by immunocytoc hemistry and Northern analysis, suggesting that TGF-alpha participates in the autocrine modulation of carcinoid growth. Co-culture of human midgut carcinoid tumours and rat fetal cholinergic neurons demonstrate d secretion of a potent neuronotrophic factor by cultured tumour cells . IGF-I and TGF-alpha may account for these neuronotrophic effects, bu t carcinoid tumours may also secrete an as yet unidentified growth fac tor. Gastric (ECL cell) carcinoids developed rapidly in Mastomys durin g hypergastrinemia due to histamine2-receptor blockade, suggesting tha t gastrin is an essential growth factor for these carcinoids.