A two-way interaction between hepatocyte growth factor and interleukin-6 in tissue invasion of lung cancer cell line
A two-way interaction between hepatocyte growth factor and interleukin-6 in tissue invasion of lung cancer cell line
复制标题
DOI：
10.1165/ajrcmb.27.2.4804
复制
发表时间：
2002-08-01
影响因子：
6.4
通讯作者：
Yamamoto, K
中科院分区：
文献类型：
--
作者：
To, Y;Dohi, M;Yamamoto, K
虽然肝细胞生长因子（HGF）和白细胞介素（IL）-6在癌细胞的侵袭中起重要作用，但这两个关键因子之间的相互作用尚未得到很好的阐明。在本研究中，我们证明了HGF和IL-6在肺癌细胞系的体外侵袭中的双向相互作用。用IL-6刺激A549肺腺癌细胞，这种处理诱导细胞中c-Met/HGF受体mRNA表达的上调。此外，IL-6增强HGF诱导的体外细胞侵袭。用抗IL-6中和抗体或抗c-Met/HGF受体阻断抗体预处理细胞可消除这种作用。我们还发现，HGF上调IL-6受体mRNA的表达在同一细胞系中，这种上调增强IL-6诱导的细胞侵袭。最后，与HGF和IL-6共刺激显示出对侵袭的累加效应，并且这种效应是由基质金属蛋白酶（MMP）-2和MMP-9的产生介导的。这些结果表明，HGF和IL-6上调彼此的受体，因此将协同增强组织侵袭。他们还提出了在某些癌细胞中细胞因子和生长因子之间的“自分泌回路”，其功能是加速其生物活性，如转移特性。
Although both hepatocyte growth factor (HGF) and interleukin (IL)-6 play important roles in invasion of cancer cells, interaction between these two critical factors has not been well elucidated. In the present study we demonstrated a two-way interaction between HGF and IL-6 in in vitro invasion of a lung cancer cell line. A549 lung adenocarcinoma cells were stimulated with IL-6, and this treatment induced an upregulation of c-Met/HGF receptor mRNA expression in the cells. In addition, IL-6 enhanced the HGF-induced in vitro cell invasion. This effect was abolished by pretreatment of the cells with either anti-IL-6 neutralizing antibody or with anti-c-Met/HGF receptor blocking antibody. We also found that HGF upregulated the expression of IL-6 receptor mRNA in the same cell line, and that this upregulation enhanced the IL-6-induced cell invasion. Finally, costimulation with HGF and IL-6 showed an additive effect on invasion, and this effect was mediated by production of matrix metalloproteinase (MMP)-2 and MMP-9. These results suggest that HGF and IL-6 upregulate each other's receptors, and thus would cooperatively enhance tissue invasion. They also suggest an "autocrine circuit" among cytokines and growth factors in certain cancer cells which functions to accelerate their biologic activities such as metastatic property.