Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells.
Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells.
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DOI：
10.1038/sj.bjc.6600331
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发表时间：
2002-06-17
影响因子：
8.8
通讯作者：
Hosokawa, M
中科院分区：
文献类型：
--
作者：
Niizeki, H;Kobayashi, M;Horiuchi, I;Akakura, N;Chen, J;Wang, J;Hamada, J;Seth, P;Katoh, H;Watanabe, H;Raz, A;Hosokawa, M
低氧压肿瘤的远处转移发生率高于高氧压肿瘤。众所周知，缺氧会诱导体内肿瘤细胞生长所需的血管生成和无氧代谢所涉及的各种基因的转录，这表明缺氧还可能诱导转移相关基因的转录。我们试图利用 DNA 微阵列系统来鉴定缺氧条件下肿瘤细胞中差异表达的转移相关基因。我们发现缺氧增强了各种癌细胞中自分泌运动因子mRNA的表达，也增强了胰腺癌细胞的随机运动。自分泌运动因子抑制剂消除了缺氧条件下运动的增加。为了探讨缺氧诱导因子-1α的作用，我们建立了缺氧诱导因子-1α转染子和显性失活缺氧诱导因子-1α转染子。缺氧诱导因子-1α和显性失活缺氧诱导因子-1α转染分别增强和抑制自分泌运动因子/磷酸六酶异构酶/神经白介素mRNA的表达和随机运动。这些结果表明，缺氧可能通过增强自分泌运动因子/磷酸六酶异构酶/神经白介素mRNA表达来促进癌细胞的转移潜力，并且破坏缺氧诱导因子-1途径可能是转移的有效治疗方法。英国癌症杂志 (2002) 86, 1914–1919。 doi:10.1038/sj.bjc.6600331 www.bjcancer.com © 2002 英国癌症研究中心
The incidence of distant metastases is higher in the tumours with low oxygen pressure than in those with high oxygen pressure. It is well known that hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumour cells in vivo, suggesting that hypoxia may also induce the transcription of metastasis-associated genes. We sought to identify the metastasis-associated genes differentially expressed in tumour cells under hypoxic conditions with the use of a DNA microarray system. We found that hypoxia enhanced the expression of autocrine motility factor mRNA in various cancer cells and also enhanced the random motility of pancreatic cancer cells. Autocrine motility factor inhibitors abrogated the increase of motility under hypoxic conditions. In order to explore the roles of hypoxia-inducible factor-1α, we established hypoxia-inducible factor-1α-transfectants and dominant negative hypoxia-inducible factor-1α-transfectants. Transfection with hypoxia-inducible factor-1α and dominant-negative hypoxia-inducible factor-1α enhanced and suppressed the expression of autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA and the random motility, respectively. These results suggest that hypoxia may promote the metastatic potential of cancer cells through the enhanced autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA expression and that the disruption of the hypoxia-inducible factor-1 pathway may be an effective treatment for metastasis. British Journal of Cancer (2002) 86, 1914–1919. doi:10.1038/sj.bjc.6600331 www.bjcancer.com © 2002 Cancer Research UK
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DOI：
10.1073/pnas.83.10.3302
发表时间：
1986-05-01
影响因子：
11.1
作者：
LIOTTA, LA;MANDLER, R;SCHIFFMANN, E
通讯作者：
SCHIFFMANN, E
影响因子：
5.3
作者：
Halterman, MW;Miller, CC;Federoff, HJ
通讯作者：
Federoff, HJ
影响因子：
64.5
作者：
ALBRECHTBUEHLER, G
通讯作者：
ALBRECHTBUEHLER, G
影响因子：
8.8
作者：
Rofstad EK;Danielsen T
通讯作者：
Danielsen T
影响因子：
4.8
作者：
Biroccio, A;Candiloro, A;Del Bufalo, D
通讯作者：
Del Bufalo, D