Abstract
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.
Highlights
The influence of lung fibroblasts on lung cancer progression is not fully understood
We investigated the interaction between lung cancer cells and lung fibroblasts within the context of the hepatocyte growth factor (HGF)/Met pathway and its impact on lung cancer progression
We found that HGF production within lung fibroblasts was stimulated by lung cancer cells and that HGF promoted the survival of lung cancer cells
Summary
The influence of lung fibroblasts on lung cancer progression is not fully understood. Kanaji et al Respiratory Research (2017) 18:118 activated protein kinase, phosphatidylinositol 3-kinaseAkt, and signal transducer and activator of transcription three pathways [5]. These pathways are known to involve cell proliferation, migration, invasion, angiogenesis, and survival [5, 6]. The significance of the HGF/Met pathway on lung cancer progression has increasingly been reported [9,10,11,12,13,14]
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