Abstract 1444: Semaphorin 6A inhibits the cell migration in lung adenocarcinoma cells

Abstract

Abstract In Taiwan, most of the female lung cancer patients are non-smokers (>90%) and most of the tumor types are adenocarcinoma. In order to discover novel molecular targets for the non-smoking female lung cancer patients in Taiwan, the paired normal and tumor lung tissues were collected from 56 female non-smoking lung cancer patients for microarray analysis. The results showed that several genes in the semaphorin family, including SEMA6A, were significantly down-regulated in the tumor tissues by Affymetrix analysis. Semaphorins are a protein family that defined into 8 different classes of protein. Semaphorin classes 3 through 7 are found in vertebrates and the classes 4 through 6 are transmembrane proteins. The semaphorin proteins have shown to play important roles in the axon guidance of the central nervous system (CNS) and peripheral nervous system (PNS). Although originally characterized as axonal guidance molecules, several studies have indicated that the semaphorins can regulate tumor growth and tumor metastasis. However, the specific mechanisms of SEMA6A in the lung cancer cells are still unclear. Therefore, the novel functions of SEMA6A in the lung cancer cells are further studied. First, the expression levels of SEMA6A in the lung cancer tissues were validated by quantitative real-time PCR and immunohistochemistry and the results showed significant down-regulation in the tumor tissues. In addition, the non-small lung cell lines, A549 and H1299, were used to further investigate the function of SEMA6A. The A549 and H1299 cells with overexpressed SEMA6A were identified and the cell membrane fraction was purified for western blot analysis. The results showed that both of the cells did not express SEMA6A proteins. Furthermore, the result of wound healing assay was shown that the A549 and H1299 cells with overexpressed SEMA6A exhibited a lower capacity to fill the gap during 24 hours incubation compared to the cells without SEMA6A overexpression. The results of transwell migration assay also showed that the A549 and H1299 cells with overexpressed SEMA6A, bur not the A549 and H1299 cells, decrease the migration ability. Our data indicated that normal lung tissues expressed more SEMA6A protein which might inhibit the migration than the cancer lung tissues. The SEMA6A receptor, plexin-A2, will be further investigated the downstream regulation of SEMA6A. In summary, our data indicated that SEMA6A could be an important factor in lung tumorgenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1444. doi:10.1158/1538-7445.AM2011-1444