Guanylate binding protein 1 (GBP-1) promotes cell motility and invasiveness of lung adenocarcinoma

Abstract

Previously, we identified molecules involved in human invasive lung adenocarcinoma, and guanylate-binding protein 1 (GBP-1) was selected for further analysis. RT-PCR of normal lung and invasive lung adenocarcinoma tissue samples showed that the relative GBP-1 expression levels normalized to GAPDH for invasive lung adenocarcinoma were three-fold higher than those for normal lung samples (P < 0.05). GBP-1 gene and protein expression levels were also higher in mesenchymal-like than in epithelial-like lung adenocarcinoma cell lines. To determine whether GBP-1 participates in lung adenocarcinoma invasion, we performed migration and wound healing assays using RERF-LC-OK cells transfected with various siRNAs. The relative migration of transfected GBP1-siRNA1 and GBP1-siRNA2 cells was significantly lower than that of transfected control-siRNA cells. The relative wound healing capacities 6 and 12 h after cells transfected with GBP1-siRNA1 and GBP1-siRNA2 were scratched were significantly lower than those of the control-siRNA cells. Immunohistochemistry of 80 patients with Stage I lung adenocarcinoma revealed that non-invasive cells were GBP-1 negative in all cases. Invasive cells were GBP-1 positive in 10 cases (12.5%) and GBP-1 negative in 70 cases (87.5%). Lymphatic-vascular invasion was positive in 20 patients (25%) and positively correlated with GBP-1 expression (P < 0.05). In conclusion, GBP-1 may enhance lung adenocarcinoma invasiveness by promoting cell motility, and control of GBP-1 expression has the potential to contribute to the development of new therapeutic strategies for lung adenocarcinoma.