PO-314 Loss of host secretory leukocyte protease inhibitor reduces lung adenocarcinoma burden

Introduction Lung cancer accounts for approximately 11.8% of all cancer diagnoses within the European Union. 1 One area of interest in lung cancer is the role of the secretory leukocyte protease inhibitor (SLPI) in lung tumorigenesis. SLPI has been identified to possess anti-bacterial, anti-protease and anti-inflammatory activity. However, SLPI levels are substantially increased in lung adenocarcinoma patient tumour tissue, with SLPI -/- mice presenting with significantly reduced pulmonary nodules in a urethane model. 2 Zelvyte et al showed a significant increase in plasma SLPI levels in lung cancer patients compared to healthy controls, and that metastatic patients exhibited increased SLPI plasma levels compared to local disease however this was not significant. 3 Material and methods Human tissue microarrays were stained for SLPI. 5 × 10 5 3 LL murine lung adenocarcinoma cells were subcutaneously (S.C.) injected into C57BL/6 WT and SLPI -/- mice. Evan’s blue dye (45 mg/kg) was intravenously injected for vessel functionality assessment. S.C. tumours were excised and stained for H and E, CD31, Ki67, TUNEL and CD45. In an experimental metastasis (I.V.) model 1 × 10 6 3 LL cells were intravenously injected into C57BL/6 WT and SLPI -/- mice. Flow cytometry and qPCR analysis was performed on S.C. tumours and experimental metastasis lung tissue. Results and discussions Human lung adenocarcinoma tissue exhibited substantially increased SLPI expression. In a subcutaneous model SLPI -/- mice exhibited significantly reduced tumour growth and cellular proliferation compared to WT mice. Tumours from SLPI -/- mice also displayed significantly reduced functional vessel number and vessel leakiness compared to WT mice. Host SLPI loss altered the immune microenvironment in both the subcutaneous and experimental metastasis model upon qPCR and flow cytometry analysis. Conclusion The findings to date highlight that SLPI may play a notable role in lung tumorigenesis. This may be due to altered neo-angiogenesis or tumour immune cell infiltration and requires further scientific investigation. These findings propose a role for SLPI as a biomarker or potential treatment target in lung cancer. References World Health Organisation, issuing body. 2012 Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed 02–13, 2018. Nukiwa T, et al. Cancer Sci 2008 May;99(5):849–855. Zelvyte I, et al. Anticancer Res 2004 Jan-Feb;24(1):241–247.