Expression of transforming growth factor alpha and its receptor in human neuroendocrine tumours.
Transforming growth-factor-alpha (TGF-alpha) 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-alpha and EGF receptors by tumour cells promote tumour-cell growth by autocrine mechanisms. In the present study we have investigated the expression of TGF-alpha and EGF receptors in human neuroendocrine tumours, including midgut carcinoid tumours, phaeochromocytomas and medullary thyroid carcinomas. TGF-alpha expression was demonstrated in biopsies of all tumours examined (n = 30) and EGF receptors in a majority of tumours by Northern analysis and/or immunocytochemistry. Expression of TGF-alpha and EGF receptors was also demonstrated in primary cultures of tumour cells. Carcinoid tumours and phaeochromocytomas in culture secreted detectable amounts of TGF-alpha into the culture medium (400-700 pM). The amount of secreted TGF-alpha could be suppressed by octreotide treatment in individual tumours. Administration of exogenous TGF-alpha stimulated carcinoid tumour growth in vitro as determined by the DNA contents of cell cultures. The growth-stimulatory effect of TGF-alpha could be partially blocked by the use of neutralizing anti-EGF receptor monoclonal antibodies (MAbs). In conclusion, several human neuroendocrine tumours express both TGF-alpha and EGF receptors in in vivo and in vitro, suggesting that TGF-alpha may regulate tumour-cell growth by autocrine mechanisms.
Department of Anatomy and Cell Biology, University of Göteborg, Sweden.
O
O
Nilsson
B
B
Wängberg
L
L
Kölby
G S
GS
Schultz
H
H
Ahlman
D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000473:pathology; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D017660:Autoreceptors / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002276:Carcinoid Tumor / Q000235:genetics / Q000556:secondary; D018276:Carcinoma, Medullary / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology; D010235:Paraganglioma / Q000235:genetics / Q000473:pathology; D010673:Pheochromocytoma / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D012186:Retroperitoneal Neoplasms / Q000235:genetics / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017660:Autoreceptors; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors