Vascular endothelial growth factor (VEGF) is expressed by neoplastic Hodgkin-Reed-Sternberg cells in Hodgkin's disease
Vascular endothelial growth factor (VEGF) is expressed by neoplastic Hodgkin-Reed-Sternberg cells in Hodgkin's disease
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DOI：
10.1002/path.1151
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发表时间：
2002-08-01
影响因子：
7.3
通讯作者：
Gatter, KC
中科院分区：
文献类型：
--
作者：
Doussis-Anagnostopoulou, IA;Talks, KL;Gatter, KC
血管内皮生长因子(VEGF)参与肿瘤血管生成，是实体瘤生长和转移潜能的重要过程。大量研究表明，在多种肿瘤中，血管内皮生长因子在mRNA和蛋白水平上均呈上调表达，并与晚期和预后有关。关于它在淋巴系统恶性肿瘤，特别是霍奇金氏病中的作用，目前的信息有限。本研究用抗CD31单抗检测了61例霍奇金病(包括经典型霍奇金病和结节淋巴细胞占优势的变异型)中血管内皮生长因子的免疫组织化学表达，并与微血管密度进行了相关性分析。在41例(70.6%)经典型霍奇金病和1例结节淋巴细胞为主的霍奇金病中，肿瘤的Reed-Sternberg细胞和Hodgkin细胞表达VEGF。染色呈胞浆，弥漫性或局灶性核旁分布。巨噬细胞始终呈阳性，而反应性淋巴细胞偶尔呈阳性。在组织间质中也观察到不同程度的细胞外染色和血管内浆染色。血管内皮生长因子的表达与何杰金氏病的亚型和微血管密度之间无统计学意义。用Reed-Sternberg细胞株L428和KM-H2在常氧和低氧条件下进行体外研究，用流式细胞仪(FACS)、细胞培养上清液免疫分析和RT-PCR检测VEGF蛋白的产生。流式细胞仪分析显示两种细胞系中都有一部分细胞与Vg1反应，细胞培养上清液中分泌的血管内皮生长因子(pg/ml/1×10(6)细胞)证实两种细胞系都有正常的缺氧产生和显著的低氧诱导(p<；0.005)。RT-PCR结果显示，两株细胞均表达血管内皮生长因子基因。综上所述，在霍奇金病中，肿瘤细胞表达血管内皮生长因子，在实体瘤中也是如此，这种表达可能是由低氧诱导的。血管内皮生长因子在反应性巨噬细胞和细胞外基质中的存在可能促进肿瘤的进展。版权所有(C)2002 John Wiley Sons，Ltd.
Vascular endothelial growth factor (VEGF) is involved in tumour angiogenesis, an important process for the growth and metastatic potential of solid tumours. Numerous studies have demonstrated up-regulation of VEGF at both mRNA and protein level in various tumours and a correlation with advanced stage and prognosis has been demonstrated in some cases. Limited information exists about its role in lymphoid malignancies and in particular, Hodgkin's disease. The present study examined the immunohistochemical expression of VEGF using the monoclonal antibody VG1 in a series of 61 cases of Hodgkin's disease, including both classical Hodgkin's disease and the nodular lymphocyte predominance variant, and correlated these results with microvessel density, using an anti-CD31 monoclonal antibody. In 41 cases (70.6%) of classical Hodgkin's disease and one of the three cases of nodular lymphocyte predominance Hodgkin's disease, the neoplastic Reed-Sternberg and Hodgkin cells expressed VEGF. The staining observed was cytoplasmic, either diffuse or with a focal paranuclear distribution. Macrophages were always positive, while reactive lymphocytes showed occasional positivity. A variable amount of strong extracellular staining was also observed in the tissue stroma and intravascular plasma staining was prominent. There was no statistically significant relationship between VEGF expression and the subtype of Hodgkin's disease or microvessel density. In vitro studies using the Reed-Sternberg cell lines L428 and KM-H2 were also performed in both normoxia and hypoxia and VEGF protein production was assessed by flow cytometry (FACS), immunoassay of cell culture supernatant, and RT-PCR. Analysis by FACS demonstrated a subset of cells in both cell lines reacting with VG1 and analysis of secreted VEGF (pg/ml per 1 X 10(6) cells) in cell culture supernatant confirmed the normoxic production in both cell lines and significant hypoxic induction (p < 0.005). Additionally, both cell lines expressed VEGF mRNA, as demonstrated using the RT-PCR method. In conclusion, neoplastic cells express VEGF in Hodgkin's disease, as is the case in solid tumours, and this expression may he induced by hypoxia. The presence of VEGF in reactive macrophages and in the extracellular matrix might facilitate tumour progression. Copyright (C) 2002 John Wiley Sons, Ltd.