Potentiation of invasive activity of hepatoma cells by reactive oxygen species is mediated by autocrine/paracrine loop of hepatocyte growth factor

Potentiation of invasive activity of hepatoma cells by reactive oxygen species is mediated by autocrine/paracrine loop of hepatocyte growth factor
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DOI:
10.1016/s0006-291x(03)00725-3
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发表时间:
2003-05-23
影响因子:
3.1
通讯作者:
Yagasaki, K
Yagasaki, K
中科院分区:
生物学4区
文献类型:
--
作者:
Miura, Y;Kozuki, Y;Yagasaki, K

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我们已经报道了活性氧(ROS)促进大鼠腹水肝癌细胞在肠系膜源性间皮细胞单层下的侵袭。为了研究这一机制,我们研究了运动因子,特别是肝细胞生长因子(HGF)的参与。大鼠腹水型肝癌细胞株AH 109 A表达HGF和c-Met mRNA。用ROS处理增加了AH 109 A中HGF mRNA的量和培养基中HGF的浓度。ROS还诱导间皮细胞中HGF基因的表达。外源性HGF可增强AH 109 A细胞的侵袭能力,但对细胞增殖无影响。ROS预处理的AH 109 A细胞侵袭能力增强,而抗HGF抗体预处理则可抑制ROS的侵袭能力。这些结果表明,AH 109 A的侵袭活性是由HGF的自分泌和旁分泌途径介导的,并且ROS通过诱导AH 109 A和间皮细胞中HGF的基因表达来增强侵袭活性。(C)2003 Elsevier Science(美国)。All rights reserved.
We have already reported that reactive oxygen species (ROS) promote rat ascites hepatoma cell invasion beneath mesentery-derived mesothelial cell monolayer. To investigate the mechanism for this, we examined the involvement of motility factors, particularly hepatocyte growth factor (HGF). Rat ascites hepatoma, cell line of AH109A expressed HGF and c-Met mRNAs. Treatment with ROS augmented amounts of HGF mRNA in AH109A and HGF concentration in the medium. ROS also induced HGF gene expression in mesothelial cells. Exogenously added HGF enhanced invasive activity of AH109A cells, but exerted no effect on proliferation. AH109A cells pretreated with ROS showed an increased invasive activity, which was cancelled by simultaneous pretreatment with anti-HGF antibody. These results suggest that the invasive activity of AH109A is mediated by the autocrine and paracrine pathways of HGF, and ROS potentiate invasive activity by inducing gene expression of HGF in AH109A and mesothelial cells. (C) 2003 Elsevier Science (USA). All rights reserved.