Hepatocyte growth factor produced in lung fibroblasts enhances non-small cell lung cancer cell survival and tumor progression.
Hepatocyte growth factor produced in lung fibroblasts enhances non-small cell lung cancer cell survival and tumor progression.
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DOI：
10.1186/s12931-017-0604-z
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发表时间：
2017-06-15
影响因子：
5.8
通讯作者：
Bandoh S
中科院分区：
文献类型：
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作者：
Kanaji N;Yokohira M;Nakano-Narusawa Y;Watanabe N;Imaida K;Kadowaki N;Bandoh S
肺成纤维细胞对肺癌进展的影响尚未完全明确。
肺成纤维细胞（HFL1、MRC5和IMR90细胞）以及非小细胞肺癌（NSCLC）来源的细胞系（A549、EBC1和HI1017）在无血清条件下培养，所得的培养基被称为“细胞条件培养基”。通过WST - 1试验评估细胞存活（活力）。采用酶联免疫吸附测定（ELISA）法测量肝细胞生长因子（HGF）的浓度。使用BALB/c - nu小鼠品系构建异种移植模型。
肺成纤维细胞条件培养基提高了所测试的三种NSCLC细胞系的存活率。肺成纤维细胞比NSCLC细胞产生更多的HGF。外源性HGF提高了NSCLC细胞的存活率。抗HGF中和抗体或Met抑制剂PHA - 665752均可抑制成纤维细胞条件培养基提高的NSCLC细胞存活率。在小鼠异种移植模型中，NSCLC细胞和成纤维细胞共同接种增强了致瘤性和肿瘤进展。PHA - 665752显著抑制了NSCLC细胞和成纤维细胞共同接种后发生的肿瘤进展。此外，NSCLC细胞刺激成纤维细胞产生HGF。
本研究提供了证据，证明成纤维细胞和NSCLC细胞通过HGF/Met信号通路相互作用，影响NSCLC细胞的存活和肿瘤进展。这些发现可能有助于开发抗癌相关成纤维细胞的治疗策略。
由于本研究不是临床试验，不需要进行试验注册。本研究不涉及任何参与者或患者。
The influence of lung fibroblasts on lung cancer progression is not fully understood. Lung fibroblasts (HFL1, MRC5, and IMR90 cells) and non-small cell lung cancer (NSCLC)-derived cell lines (A549, EBC1, and HI1017) were cultured under serum-free conditions, and the resulting culture media were designated “cell-conditioned media”. Cell survival (viability) was assessed by WST-1 assay. Concentrations of hepatocyte growth factor (HGF) were measured by ELISA. The BALB/c-nu mouse strain was used for the xenograft model. Lung fibroblast-conditioned media enhanced the survival of the three NSCLC cell lines tested. HGF was produced to a greater extent by lung fibroblasts than NSCLC cells. Exogenous HGF enhanced the survival of NSCLC cells. Either an anti-HGF neutralizing antibody or the Met inhibitor PHA-665752 inhibited the fibroblast-conditioned media-enhanced survival of NSCLC cells. The co-inoculation of mice with NSCLC cells and fibroblasts enhanced tumorigenicity and tumor progression in a mouse xenograft model. PHA-665752 significantly inhibited tumor progression that occurred after the co-inoculation of NSCLC cells and fibroblasts. In addition, HGF production by fibroblasts was stimulated by NSCLC cells. The current study provides evidence for an interaction between fibroblasts and NSCLC cells via the HGF/Met signaling pathway, which affects NSCLC cell survival and tumor progression. These findings may contribute to the development of anti-cancer-associated fibroblast therapeutic strategies. No trial registration is required because this study is not a clinical trial. This study does not include any participants or patients.