Human endocrine gland-derived vascular endothelial growth factor: Expression early in development and in Leydig cell tumors suggests roles in normal and pathological testis angiogenesis
Human endocrine gland-derived vascular endothelial growth factor: Expression early in development and in Leydig cell tumors suggests roles in normal and pathological testis angiogenesis
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DOI：
10.1210/jc.2003-032024
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发表时间：
2004-08-01
影响因子：
5.8
通讯作者：
Ferrara, N
中科院分区：
文献类型：
--
作者：
Samson, M;Peale, FV;Ferrara, N
血管生成对于肿瘤的生长和转移是必不可少的。一种新的人血管生成有丝分裂原，内分泌腺衍生的血管内皮生长因子（EG-VEGF），最近已被确定，其表达模式仅限于内分泌腺，在睾丸中的表达最高。我们使用原位杂交和新产生的单克隆抗体，研究EG-VEGF在正常人产前和成人睾丸和48人睾丸肿瘤的不同亚型的表达。我们发现EG-VEGF在人胎儿睾丸中从14周开始表达，直至出生。在成年睾丸中，EG-VEGF仅在Leydig细胞中强表达。在睾丸肿瘤中，EG-VEGF在间质细胞肿瘤中特异性表达，而生殖细胞来源的肿瘤，包括原位癌、卵巢癌和非卵巢癌性生殖细胞肿瘤，对此抗原呈阴性。相反，VEGF，另一个强大的血管生成因子，在乳腺癌中表达，但在Leydig细胞肿瘤中非常弱。有趣的是，我们发现睾丸间质细胞瘤的血管表面密度比睾丸间质细胞瘤高3.2倍。这些研究结果表明，人EG-VEGF可能在睾丸内分泌发育早期和成年睾丸以及Leydig细胞肿瘤生长中的血管生成中发挥作用。
Angiogenesis is essential for tumor growth and metastasis. A new human angiogenic mitogen, endocrine gland-derived vascular endothelial growth factor (EG-VEGF), has been recently identified; its expression pattern is restricted to endocrine glands, with the highest expression in testis. We used in situ hybridization and newly generated monoclonal antibodies to investigate the expression of EG-VEGF in normal human prenatal and adult testis and in 48 human testicular tumors of different subtypes. We found that EG-VEGF was expressed from 14 wk until birth in human fetal testis. In the adult testis, EG-VEGF was strongly expressed only in Leydig cells. In testicular tumors, EG-VEGF was expressed specifically in Leydig cell tumors, whereas germ cell-derived neoplasms, including carcinoma in situ, seminoma, and nonseminomatous germ cell tumors, were negative for this antigen. In contrast, VEGF, another powerful angiogenic factor, was expressed in seminoma, but very weakly in Leydig cell tumors. Interestingly, we found that Leydig cell tumors presented vessel surface density 3.2-fold higher than seminoma. These findings argue that human EG-VEGF may play a role in angiogenesis both during the early endocrine development of testis and in the adult testis as well as in Leydig cell tumor growth.