Vascular endothelial growth factor expression in human neuroblastoma: Up‐regulation by hypoxia

Vascular endothelial growth factor expression in human neuroblastoma: Up‐regulation by hypoxia
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人神经母细胞瘤中血管内皮生长因子的表达:缺氧上调

DOI:
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发表时间:
1999
影响因子:
6.4
通讯作者:
Lothar Schweigerer
Lothar Schweigerer
中科院分区:
医学1区
文献类型:
--
作者:
J. Rössler;S. Breit;W. Havers;Lothar Schweigerer

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血管生成的增强显然导致了人神经母细胞瘤的不良临床结局,但其机制仍不清楚。我们在这里报告,培养的人神经母细胞瘤细胞表达一种生物活性的内皮细胞生长因子与血管生成刺激因子血管内皮生长因子(VEGF)无区别。VEGF存在于神经母细胞瘤中,而不是血管内皮细胞中,而相应的VEGF受体(Flt-1和Flk-1/KDR)在内皮细胞中表达,而不是神经母细胞瘤细胞。神经母细胞瘤细胞暴露于缺氧诱导生物活性VEGF显著增加。VEGF也存在于人神经母细胞瘤标本中,在明显缺氧的神经母细胞瘤细胞中有大量VEGF,最终积聚在肿瘤微血管中。我们的研究结果表明,VEGF(i)存在于人神经母细胞瘤中,(ii)通过肿瘤缺氧上调,(iii)可能通过旁分泌机制刺激神经母细胞瘤血管生成,从而促进人神经母细胞瘤的进展。我们认为,抑制VEGF活性可能代表了一种新的方法治疗人神经母细胞瘤。Int. J. Cancer 81:113-117,1999.© 1999 Wiley利斯公司
Enhanced angiogenesis apparently contributes to the poor clinical outcome of human neuroblastoma, but the mechanisms have remained unclear. We report here that cultured human neuroblastoma cells express a bioactive endothelial cell growth factor indistinguishable from the angiogenesis stimulator vascular endothelial growth factor (VEGF). VEGF is present in neuroblastoma but not vascular endothelial cells, whereas the corresponding VEGF receptors (Flt‐1 and Flk‐1/KDR) are expressed in endothelial but not neuroblastoma cells. Exposure of neuroblastoma cells to hypoxia induces a marked increase in bioactive VEGF. VEGF is also present in human neuroblastoma specimens, with substantial amounts in apparently hypoxic neuroblastoma cells, eventually accumulating in tumor microvessels. Our results indicate that VEGF (i) is present in human neuroblastomas, (ii) is up‐regulated by tumor hypoxia and (iii) may stimulate neuroblastoma angiogenesis by paracrine mechanisms, thereby contributing to the progression of human neuroblastomas. We suggest that inhibition of VEGF activity may represent a novel approach for the therapy of human neuroblastoma. Int. J. Cancer 81:113–117, 1999. © 1999 Wiley‐Liss, Inc.
急性淋巴细胞白血病儿童骨髓中肿瘤血管生成的谱。
DOI: --
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