Abstract 2853: Cell motility and invasiveness are promoted by guanylate binding protein 1, GBP-1 in lung adenocarcinoma

Abstract

Abstract Previously, we identified candidate molecules involved in human lung adenocarcinoma progression from non-invasive to invasive tumor by comparing gene expression profiles of each component in the same tumor using laser microdissection and DNA microarray analysis. Among them, guanylate-binding protein 1 (GBP-1) was selected for further analysis because RT-PCR for normal lung and invasive human lung adenocarcinoma tissue samples showed that the relative GBP-1 gene expression levels normalized to GAPDH for invasive lung adenocarcinoma were approximately three-fold higher than those for normal lung samples. In addition, GBP-1 gene and protein expression levels were also higher in mesenchymal-like than in epithelial-like lung cancer cell lines. To determine whether GBP-1 is involved in lung adenocarcinoma cell motility and invasion, we performed migration and wound healing assays using RERF-LC-OK, human lung adenocarcinoma cells transfected with siRNAs. The relative migration of transfected GBP1-siRNA cells was significantly lower than that of control-siRNA cells. The relative wound healing capacities were assessed after scratching. Cells transfected with GBP1-siRNAs were also significantly lower than those of the control-siRNAcells. Moreover, Immunohistochemistry of 80 patients with stage I lung adenocarcinoma demonstrated that non-invasive component cells showed clearly negative GBP-1 expression in all cases. On the other hand, invasive component 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 might enhance lung adenocarcinoma cell motility and invasiveness and controlling of GBP-1 expression has the potential to contribute to the development of novel therapeutic strategies for lung adenocarcinoma. Citation Format: Takahiro Mimae, Ichiko Yamakita, Yasuhiro Tsutani, Yoshihiro Miyata, Akihiko Ito, Morihito Okada. Cell motility and invasiveness are promoted by guanylate binding protein 1, GBP-1 in lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2853.