Abstract 5199: The biological importance of LRIG1 in lung cancer.

Abstract

Abstract Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is an endogenous inhibitor of epidermal growth factor receptor (EGFR) signaling. LRIG1 is down-regulated in several forms of human cancer. The LRIG gene family also includes LRIG2 and LRIG3. EGFR signaling is important in non-small cell lung cancer (NSCLC) and EGFR tyrosine kinase inhibitors are today considered standard treatment in patients with advanced disease. Since smoking recently was reported to down-regulate LRIG1 gene expression in lung epithelium and squamous cell carcinoma of the lung, the LRIG family of proteins may be important in lung cancer. The objective of the present study was to investigate if LRIG is a prognostic factor in non-small cell lung cancer (NSCLC) and if LRIG1 have any effects of lung cancer growth in vivo and in vitro. In the present study we analyzed the LRIG protein expression by immunohistochemistry in a tissue microarray (TMA) from surgically treated patients with NSCLC (n=366). To study the effect of LRIG1 expression on tumor growth, an animal model was used. Transgenic mice with an inducible EGFR L858R mutation were crossbred with LRIG1 knockout mice and tumor growth was assessed with micro-MRI. The impact of ectopic LRIG1 expression on lung cancer cell proliferation was studied in vitro. In the TMA, patients with high LRIG1 expression had a significantly longer median survival than negative cases (p=0.012). In the animal model, tumor progression was significantly faster in LRIG1 knockout mice 60 days after tumor induction (p=0.025) indicating that LRIG1 is of importance in the early tumor progression. Transient ectopic expression of LRIG1 inhibited lung cancer cell proliferation in vitro. In summary, LRIG1 was a positive prognostic factor in lung cancer and LRIG1 expression inhibited lung cancer growth in vivo and in vitro. This suggests that LRIG1 is of biological importance in lung cancer and that further studies of LRIG1 as a biomarker and tumor suppressor in lung cancer are warranted. Citation Format: Samuel Kvarnbrink, Karolina Edlund, Johan Botling, Patrick Micke, Roger Henriksson, Håkan Hedman, Mikael Johansson. The biological importance of LRIG1 in lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5199. doi:10.1158/1538-7445.AM2013-5199