Borg S A, Kerry K E, Royds J A, Battersby R D, Jones T H
Hormone and Vascular Group, Academic Unit of Endocrinology, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield S10 2RX, UK.
Eur J Endocrinol. 2005 Feb;152(2):293-300. doi: 10.1530/eje.1.01843.
Vascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor involved in the neovascularisation of solid tumours. Regulatory molecules include cytokines and growth factors. Interleukin (IL)1 and IL6 have both been shown to regulate VEGF levels in a variety of tissues. The role of cytokines in the pathogenesis of pituitary tumours remains unclear. We have examined the expression of VEGF and its relationships with IL1 and IL6 in the human pituitary tumour cell line HP75 and a series of human pituitary tumours. We have also looked at the relationship of tumour volume and invasive status to VEGF secretion.
Surgically resected tumours were routinely cultured in single-cell suspension at 200 K/well (standard unit for culture of dispersed primary pituitary adenoma cells). We measured VEGF, IL1 alpha and IL6 levels by ELISA. Tumour volume and invasion grade were assessed by preoperative magnetic resonance imaging.
VEGF was detected in conditioned medium of HP75 cells (900+/-52 pg/ml) and in 82% of tumours tested (range 26-16 464 pg/ml). Tumour volume and secretion of VEGF were significantly associated with levels of IL6 (volume, P = 0.056; VEGF, P < 0.001 (P values based on Spearman's test)) and IL1 alpha produced (volume, P < 0.005; VEGF, P < 0.001). Invasive tumours showed a higher basal secretion of VEGF that that of the non-invasive type; however, this difference was not significant. Addition of exogenous IL1 alpha, but not IL6, significantly increased VEGF production.
The significant associations between VEGF and the levels of IL6 and IL1 alpha suggest an important role for these cytokines in the development of these tumours.
血管内皮生长因子（VEGF）被认为是参与实体瘤新生血管形成的最重要的血管生成因子。调节分子包括细胞因子和生长因子。白细胞介素（IL）-1和IL-6均已被证明可调节多种组织中的VEGF水平。细胞因子在垂体瘤发病机制中的作用仍不清楚。我们研究了VEGF在人垂体瘤细胞系HP75和一系列人垂体瘤中的表达及其与IL-1和IL-6的关系。我们还研究了肿瘤体积和侵袭状态与VEGF分泌的关系。
手术切除的肿瘤常规以单细胞悬液形式在200K/孔（分散的原发性垂体腺瘤细胞培养的标准单位）中培养。我们通过酶联免疫吸附测定法测量VEGF、IL-1α和IL-6水平。术前磁共振成像评估肿瘤体积和侵袭分级。
在HP75细胞的条件培养基中检测到VEGF（900±52 pg/ml），在82%的测试肿瘤中也检测到VEGF（范围为26-16464 pg/ml）。肿瘤体积和VEGF分泌与IL-6水平（体积，P = 0.056；VEGF，P < 0.001（P值基于Spearman检验））以及产生的IL-1α显著相关（体积，P < 0.005；VEGF，P < 0.001）。侵袭性肿瘤的VEGF基础分泌高于非侵袭性肿瘤；然而，这种差异不显著。添加外源性IL-1α而非IL-6可显著增加VEGF产生。
VEGF与IL-6和IL-1α水平之间的显著关联表明这些细胞因子在这些肿瘤的发生发展中起重要作用。
