Melanoma-associated expression of vascular endothelial growth factor and its receptors FLT-1 and KDR
Melanoma-associated expression of vascular endothelial growth factor and its receptors FLT-1 and KDR
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DOI：
10.1007/s004320050325
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发表时间：
1999-11-01
影响因子：
3.6
通讯作者：
Hossfeld, DK
中科院分区：
文献类型：
--
作者：
Graeven, U;Fiedler, W;Hossfeld, DK
血管内皮生长因子（VEGF）及其两种受体flt-1和KDR在正常人类黑素细胞、表达类人猿病毒40tgene （SV40T）的转化黑素细胞以及源自原发和转移性病变的黑色素瘤细胞中的表达模式进行了评估。在大多数原发性和转移性黑色素瘤细胞系以及sv40t转化的黑色素细胞中，均观察到VEGF、flt-1和KDR mRNA和蛋白的组成性表达。胰岛素和胎牛血清等外源性生长因子进一步增强了VEGF在黑色素瘤细胞系中的表达。相比之下，新生儿黑素细胞不表达VEGF或VEGF受体，外源性生长因子不能诱导VEGF表达。外源性VEGF对黑色素瘤细胞增殖或VEGF转录靶点尿激酶型纤溶酶原激活物的产生没有显著影响。在转移性黑色素瘤细胞系WM164中，通过转染VEGF反义构建体下调VEGF表达同样不会影响转染细胞在存在或不存在外源性VEGF的情况下的增殖。综上所述，VEGF及其受体的共表达是黑色素瘤发展过程中的肿瘤相关现象。然而，VEGF的产生并不支持黑色素瘤细胞系的自分泌增殖。
The expression patterns of vascular endothelial growth factor (VEGF) and its two receptors, flt-1 and KDR, were assessed in normal human melanocytes, transformed melanocytes expressing the simian virus 40 Tgene (SV40T), and melanoma cells derived from primary and metastatic lesions. Constitutive expression of VEGF, flt-1, and KDR mRNA and proteins was observed in the majority of primary and metastatic melanoma cell lines, and in SV40T-transformed melanocytes. VEGF expression in melanoma cell lines was further enhanced by exogenous growth factors including insulin and fetal calf serum. By contrast, neonatal melanocytes did not express VEGF or VEGF receptors and VEGF expression could not be induced by exogenous growth factors. Exogenous VEGF had no significant effects on melanoma cell proliferation or on production of a transcriptional target for VEGF, urokinase-type plasminogen activator. Down-regulation of VEGF expression in the metastatic melanoma cell line WM164 through transfection of a VEGF antisense construct similarly did not affect proliferation of the transfected cells in the presence or absence of exogenous VEGF. In summary, coexpression of VEGF and its receptors is a tumor-associated phenomenon in melanoma development. However VEGF production does not support autocrine proliferation of the melanoma cell lines tested.