Nilsson O, Wängberg B, Kölby L, Schultz G S, Ahlman H
Department of Anatomy and Cell Biology, University of Göteborg, Sweden.
Int J Cancer. 1995 Mar 3;60(5):645-51. doi: 10.1002/ijc.2910600514.
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.
转化生长因子-α（TGF-α）是一种由50个氨基酸组成的多肽，它能与表皮生长因子（EGF）受体结合并刺激细胞生长。有研究表明，肿瘤细胞中TGF-α和EGF受体的产生增加，通过自分泌机制促进肿瘤细胞生长。在本研究中，我们调查了TGF-α和EGF受体在人类神经内分泌肿瘤中的表达情况，这些肿瘤包括中肠类癌、嗜铬细胞瘤和甲状腺髓样癌。通过Northern分析和/或免疫细胞化学方法，在所有检测的肿瘤活检组织（n = 30）中均证实了TGF-α的表达，大多数肿瘤中检测到了EGF受体的表达。在肿瘤细胞的原代培养物中也证实了TGF-α和EGF受体的表达。培养的类癌和嗜铬细胞瘤可向培养基中分泌可检测量的TGF-α（400 - 700 pM）。在个别肿瘤中，奥曲肽治疗可抑制TGF-α的分泌量。通过细胞培养物的DNA含量测定，外源性TGF-α的给予可刺激类癌在体外生长。使用中和性抗EGF受体单克隆抗体（MAb）可部分阻断TGF-α的生长刺激作用。总之，几种人类神经内分泌肿瘤在体内和体外均表达TGF-α和EGF受体，提示TGF-α可能通过自分泌机制调节肿瘤细胞生长。
