Paraneoplastic syndromes associated with lung cancer

Purpose The clinical features of patients with advanced non-small cell lung cancer (NSCLC) and interstitial lung disease (ILD) have not fully been elucidated. This study aimed to investigate the clinical features of these patients, particularly with idiopathic pulmonary fibrosis (IPF). Methods Data on 218 patients with pathologically confirmed diagnoses of NSCLC who had been treated with chemotherapy and/or molecular targeted therapy were retrospectively analyzed for progression-free survival (PFS), overall survival (OS), responses to first-line therapy, and incidence of acute exacerbations (AEs). Results Fifty-three of the 218 patients were diagnosed with ILD, and 34 of them with IPF. The frequency of epidermal growth factor receptor (EGFR) mutation was significantly lower in ILD and IPF patients than in non-ILD patients (2 or 0 vs. 32 %, respectively). Median PFS and OS were significantly shorter in both ILD and IPF patients than in non-ILD patients (118, 92, and 196 days for PFS, and 267, 223, and 539 days for OS, respectively). Multivariate analysis showed that poor performance status, absence of EGFR mutation, and presence of IPF were poor prognostic factors for PFS and OS. Disease control rate (DCR) was significantly lower in ILD and IPF patients than in non-ILD patients regardless of the presence of EGFR mutation (67 or 53 vs. 85 %, respectively). The incidence of AEs of ILD was significantly higher during chemotherapy with docetaxel-containing regimens (seven of 38; 18.4 %). Conclusions Both IPF and ILD were associated with lower EGFR positivity, lower DCR, and shorter PFS and OS in advanced NSCLC patients.

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.