Malkomes P, Oppermann E, Bechstein W O, Holzer K
Department of General Surgery, University Hospital of Frankfurt, Frankfurt, Germany.
Exp Clin Endocrinol Diabetes. 2013 Jan;121(1):6-13. doi: 10.1055/s-0032-1327634. Epub 2013 Jan 17.
Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis and is involved in tumor development. To date, the role of VEGF in benign diseases of the thyroid is not well known. The purpose of the present study is to determine the expression of VEGF and its receptors in primary cultures of human thyrocytes.
50 patients with uninodular (n=11), multinodular (n=15), recurrent goiter (n=14) and Graves' disease (n=10) were enrolled. Nodular and corresponding paranodular tissue was obtained after surgery and investigated. RNA and protein were extracted from primary thyrocyte cultures. PCR, western blot and ELISA were performed to evaluate VEGF isoforms and VEGF receptor 1 and 2.
Significantly increased transcription and protein expression of VEGF and its receptors were detected in nodular tissue of uninodular and recurrent goiter compared to the corresponding normal tissue. Active secretion of VEGF by thyrocytes was confirmed by ELISA. In multinodu-lar goiter, no difference could be found between nodular and corresponding paranodular tissue in terms of expression of VEGF or its receptors. Furthermore, we found the highest levels of VEGF and its receptors in tissue obtained from patients with Graves' disease.
Increased expression of VEGF and its receptors might be crucial in the proliferation of thyrocytes and therefore may contribute to the development of goiter and goiter recurrence.
血管内皮生长因子(VEGF)是血管生成的关键调节因子,参与肿瘤发展。迄今为止,VEGF在甲状腺良性疾病中的作用尚不明确。本研究的目的是确定VEGF及其受体在人甲状腺细胞原代培养中的表达。
纳入50例患者,其中单结节性甲状腺肿患者11例、多结节性甲状腺肿患者15例、复发性甲状腺肿患者14例、格雷夫斯病患者10例。术后获取结节及相应的结节旁组织并进行研究。从甲状腺细胞原代培养物中提取RNA和蛋白质。采用聚合酶链反应(PCR)、蛋白质免疫印迹法(western blot)和酶联免疫吸附测定(ELISA)评估VEGF异构体以及VEGF受体1和2。
与相应正常组织相比,在单结节性和复发性甲状腺肿的结节组织中检测到VEGF及其受体的转录和蛋白表达显著增加。ELISA证实甲状腺细胞可活跃分泌VEGF。在多结节性甲状腺肿中,结节组织与相应结节旁组织在VEGF或其受体表达方面未发现差异。此外,我们发现格雷夫斯病患者组织中VEGF及其受体水平最高。
VEGF及其受体表达增加可能在甲状腺细胞增殖中起关键作用,因此可能促成甲状腺肿的发生和复发。