Hepatocyte growth factor produced in lung fibroblasts enhances non-small cell lung cancer cell survival and tumor progression

Respiratory Research

Research

Norimitsu Kadowaki¹  Shuji Bandoh¹  Nobuhiro Kanaji¹  Naoki Watanabe¹  Yuko Nakano-Narusawa²  Katsumi Imaida²  Masanao Yokohira² 

[1] Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, 761-0793, Kagawa, Japan;Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan;

关键词: Lung cancer;    Fibroblast;    Cancer-associated fibroblast;    Hepatocyte growth factor;    PHA-665752;    Met;    Xenograft;    Tumorigenicity;   

DOI  :  10.1186/s12931-017-0604-z

 received in 2017-01-17, accepted in 2017-06-07,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe influence of lung fibroblasts on lung cancer progression is not fully understood.MethodsLung 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.ResultsLung 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.ConclusionsThe 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.Trial registrationNo trial registration is required because this study is not a clinical trial. This study does not include any participants or patients.

【 授权许可】

CC BY   
© The Author(s). 2017