Hypoxia-induced metastasis of human melanoma cells: involvement of vascular endothelial growth factor-mediated angiogenesis.
Hypoxia-induced metastasis of human melanoma cells: involvement of vascular endothelial growth factor-mediated angiogenesis.
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DOI：
10.1038/sj.bjc.6690586
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发表时间：
1999-08
影响因子：
8.8
通讯作者：
Danielsen T
中科院分区：
文献类型：
--
作者：
Rofstad EK;Danielsen T
暴露于缺氧的肿瘤细胞已被证明上调血管内皮生长因子（VEGF）的表达。本研究的目的是探讨缺氧诱导的VEGF上调是否会导致人黑色素瘤细胞转移效率的增加。研究中包括两种黑素瘤细胞系，一种在有氧条件下显示高（A-07）VEGF分泌，另一种显示低（D-12）VEGF分泌。将细胞培养物在体外暴露于缺氧（氧浓度< 10 ppm），并在BALB/c-nu/nu小鼠中评估转移效率，即肺定殖效率，以及可移植性和血管生成潜力。这两种细胞系显示显着增加VEGF分泌缺氧条件下，通过酶联免疫吸附测定。D-12细胞暴露于缺氧后显示出增加的转移效率、可移植性和血管生成潜力。随着缺氧时间的延长，转移效率增加，随着复氧时间的延长，转移效率下降。另一方面，A-07细胞在暴露于缺氧后显示出不变的转移效率、可移植性和血管生成潜力。两种细胞系在用针对VEGF的中和抗体处理的小鼠中显示出显著降低的转移效率和血管生成潜力。这些结果表明：（a）在常氧条件下，VEGF是低表达黑色素瘤血管生成速率的限制因素，而不是高表达黑色素瘤血管生成速率的限制因素;（B）短暂缺氧可能通过上调VEGF表达促进低表达黑色素瘤转移的发展，从而增强肿瘤细胞的血管生成潜力。© 1999癌症研究运动
Tumour cells exposed to hypoxia have been shown to up-regulate the expression of vascular endothelial growth factor (VEGF). The purpose of the present work was to investigate whether hypoxia-induced VEGF up-regulation can result in increased metastatic efficiency of human melanoma cells. Two melanoma lines, one showing high (A-07) and the other showing low (D-12) VEGF secretion under aerobic conditions, were included in the study. Cell cultures were exposed to hypoxia (oxygen concentrations < 10 ppm) in vitro and metastatic efficiency, i.e. lung colonization efficiency, as well as transplantability and angiogenic potential were assessed in BALB/c-nu/nu mice. Both cell lines showed significantly increased VEGF secretion under hypoxic conditions as measured by enzyme-linked immunosorbent assay. The D-12 cells showed increased metastatic efficiency, transplantability and angiogenic potential following exposure to hypoxia. The metastatic efficiency increased with the duration of the hypoxia treatment and decreased with the time after reoxygenation. The A-07 cells on the other hand showed unchanged metastatic efficiency, transplantability and angiogenic potential following exposure to hypoxia. Both cell lines showed significantly decreased metastatic efficiency and angiogenic potential in mice treated with neutralizing antibody against VEGF. These results suggest that (a) VEGF is a limiting factor for the rate of angiogenesis in low but not in high VEGF-expressing melanomas under normoxic conditions and (b) transient hypoxia might promote the development of metastases in low VEGF-expressing melanomas by upregulating the expression of VEGF and hence enhancing the angiogenic potential of the tumour cells. © 1999 Cancer Research Campaign