View Abstract

A7096 - High Expression of Integrin Alpha 11 Is Associated with Tumor Progression and Postoperative Recurrence
Author Block: T. Ando1, H. Kage1, K. Maemura1, N. Hiyama2, T. Sakatani1, Y. Amano1, K. Watanabe1, J. Nakajima2, T. Nagase1, D. Takai3; 1Department of Respiratory Medicine, The University of Tokyo, Tokyo, Japan, 2Department of Cardiothoracic Surgery, The University of Tokyo, Tokyo, Japan, 3Department of Clinical Laboratory, The University of Tokyo, Tokyo, Japan.
[Rationale] Integrins are transmembrane proteins that mediate cell adhesion to extracellular matrix. In addition, integrins activate a variety of intracellular signaling cascades. Whereas aberrant expression of integrins in cancer cells are considered to promote tumor progression and metastasis, functions of integrins in lung cancer have not been studied in detail. The aim of this study was to determine whether and how aberrant integrin expression in lung adenocarcinoma leads to worse outcomes. [Methods] We searched for membrane proteins aberrantly expressed in lung cancer using publicly available human lung cancer microarray data, and found that they were enriched for integrins. We measured messenger RNA expression of integrins by quantitative RT-PCR in 73 samples collected from lung adenocarcinoma patients who had undergone surgical resection. We assigned patients to high and low expression groups according to the expression level of integrin alpha 11 (ITGA11) and analyzed clinical features, pathological stage, tumor size, vascular invasion, lymphatic invasion and postoperative recurrence-free survival. Cell proliferation and migration in human cell lines that overexpressed ITGA11 were examined by using Cell Counting Kit-8 (CCK-8) and wound healing assay. [Results] Among 73 cases, 36 were female and 37 were male, with a mean age of 68 years, ranging from 36 to 83 years. Expression of ITGA11 was low in normal lung tissue. High expression of ITGA11 in lung adenocarcinoma was associated with higher stage (p = 0.031) and lower recurrence-free survival (p = 0.025). While expression of ITGA11 was not related to tumor size or lymphatic invasion, adenocarcinoma with vascular invasion had significantly higher ITGA11 expression (p = 0.047). Human cell lines that overexpressed ITGA11 had no effect on cell proliferation but resulted in increased migration capacity. [Conclusion] High expression of ITGA11 in adenocarcinoma was associated with higher cancer stage, vascular invasion, and postoperative recurrence. Our findings in human cell lines suggest that ITGA11 plays a significant role in cancer invasion, which may lead to higher recurrence rate.