Expression of transforming growth factor alpha and its receptor in human neuroendocrine tumours

Abstract

Transforming growth‐factor‐α (TGF‐α) is a 50‐amino‐acid polypeptide that binds to the epidermal growth factor (EGF) receptor and stimulates cell growth. It has been suggested that enhanced production of TGF‐α and EGF receptors by tumour cells promote tumour‐cell growth by autocrine mechanisms. In the present study we have investigated the expression of TGF‐α and EGF receptors in human neuroendocrine tumours, including midgut carcinoid tumours, phaeochromocytomas and medullary thyroid carcinomas. TGF‐α expression was demonstrated in biopsies of all tumours examined (n = 30) and EGF receptors in a majority of tumours by Northern analysis and/or immunocy‐tochemistry. Expression of TGF‐α and EGF receptors was also demonstrated in primary cultures of tumour cells. Carcinoid tumours and phaeochromocytomas in culture secreted detectable amounts of TGF‐α into the culture medium (400–700 pM). The amount of secreted TGF‐α could be suppressed by octreotide treatment in individual tumours. Administration of exogenous TGF‐α stimulated carcinoid tumour growth in vitro as determined by the DNA contents of cell cultures. The growth‐stimulatory effect of TGF‐α could be partially blocked by the use of neutralizing anti‐EGF receptor monoclonal antibodies (MAbs). In conclusion, several human neuroendocrine tumours express both TGF‐α and EGF receptors in in vivo and in vitro, suggesting that TGF‐α may regulate tumour‐cell growth by autocrine mechanisms.