Neutrophils enhance invasion activity of human cholangiocellular carcinoma and hepatocellular carcinoma cells:: An in vitro study

Neutrophils enhance invasion activity of human cholangiocellular carcinoma and hepatocellular carcinoma cells:: An in vitro study
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DOI:
10.1111/j.1440-1746.2004.03575.x
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发表时间:
2005-02-01
影响因子:
4.1
通讯作者:
Okazaki, K
Okazaki, K
中科院分区:
医学3区
文献类型:
--
作者:
Imai, Y;Kubota, Y;Okazaki, K

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背景和目的:肿瘤-间质相互作用参与多种类型癌症的肿瘤侵袭机制。然而,人们对癌细胞和中性粒细胞之间的相互作用知之甚少。在本研究中,我们检测了中性粒细胞对体外癌细胞侵袭活性的影响。还评估了肝细胞生长因子(HGF)作为介质的作用。方法:使用Matrigel侵袭室,评估HuCC-T1人胆管细胞癌细胞和HepG2肝癌细胞响应重组HGF或中性粒细胞的侵袭活性。结果:重组HGF剂量依赖性地增加HuCC-T1和HepG2细胞的侵袭活性。中性粒细胞显着增强这些细胞的侵袭活性,抗HGF抗体将其抑制至各自的基础水平。癌细胞不分泌HGF。在 HuCC-T1 或 HepG2 细胞的肿瘤条件培养基 (TCM) 中培养的中性粒细胞分泌显着水平的 HGF 蛋白,而不增加 HGF mRNA 表达。对HuCC-T1或HepG2细胞进行中药加热或超滤处理,提示癌细胞来源的HGF诱导剂是分子量大于30 000的某些蛋白质。结论:本研究表明,HuCC-T1/HepG2癌细胞与中性粒细胞在肿瘤侵袭过程中存在相互作用,通过中性粒细胞来源的HGF介导的旁分泌调节。 (C) 2005 年布莱克威尔出版亚洲有限公司。
Background and Aim: Tumor-mesenchymal interactions are involved in the mechanism of tumor invasion in several types of carcinoma. Mutual interactions between carcinoma cells and neutrophils, however, have been poorly understood. In the present study we examined the effect of neutrophils on invasion activities of carcinoma cells in vitro. Role of hepatocyte growth factor (HGF) as a mediator was also evaluated.Methods: Using a Matrigel invasion chamber, invasion activities of HuCC-T1 human cholangiocellular carcinoma cells and HepG2 hepatocellular carcinoma cells in response to recombinant HGF or neutrophils were evaluated.Results: Recombinant HGF dose-dependently increased invasion activities of HuCC-T1 and HepG2 cells. Neutrophils significantly enhanced invasion activities of these cells, which were suppressed to the respective basal levels with anti-HGF antibody. The carcinoma cells did not secrete HGF. Neutrophils cultivated in tumor condition medium (TCM) of HuCC-T1 or HepG2 cells secreted a significant level of HGF protein without increasing HGF mRNA expression. Treatment with heat or ultrafiltration of TCM of HuCC-T1 or HepG2 cells suggested carcinoma cell-derived HGF inducer(s) to be certain protein(s) with a molecular weight of more than 30 000.Conclusions: The present study suggests the presence of mutual interactions between HuCC-T1/ HepG2 carcinoma cells and neutrophils in tumor invasion via paracrine regulation mediated by neutrophil-derived HGF. (C) 2005 Blackwell Publishing Asia Pty Ltd.