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Lung Cancer: Lung Cancer IV |

TLR9 is a Cancer Stem Cell Maintenance Marker in Non-small Cell Lung Cancer FREE TO VIEW

Fengying Wu, MD; Shan Shan; Yang Han; Tao Ren
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Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(4_S):A323. doi:10.1016/j.chest.2016.02.336
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SESSION TITLE: Lung Cancer IV

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: Accumulating evidences have been identified that CSCs play a pivotal role in tumor regeneration, metastasis and drug resistance in lung cancer. Toll-like receptor 9 (TLR9), when activated by its ligands CpG oligodinucleotides (CpG-ODN), can trigger IKK/NF-kB, MAPK/AP-1 and PI3K/Akt signal pathways, and finally contribute to the growth and metastasis of lung cancer cells. Most recently, Andreas and colleagues identified that TLR9 is a critical functional marker for glioma stem cells and a target for the delivery of efficacious glioma treatment. While the role of TLR9 in other stem cells, including lung cancer stem cells, haven’t been elucidated until now. Thus this study aims to investigate the role of TLR9 in lung CSC.

METHODS: CSCs were isolated from cell lines and patient tissues by CD133 and ALDH labeled flow cytometry. Western blot and Immunofluorescence were used to detect constitutive expression of TLR9. Then we down regulated the expression of TLR9 in CSCs. The changes of cell proliferation, invasion, tumorigenesis, drug resistance and other stem cell markers or drug transporters gene expression were investigated after TLR9 downregulated. The association of TLR9 expression with patient survival was analyzed by SPSS.

RESULTS: We found that TLR9 are constitutively overexpressed on lung CSCs derived from lung cancer cell lines and patients’ tissue as compared with non-stem cells. Furthermore, knocking down of TLR9 in lung CSCs exhibit inhibited capacity for proliferation, invasion, tumorigenesis and resistance to chemotherapy drugs. Moreover, cell cycle was arrested at G2/M stages and more apoptosis existed after TLR9 expression decreased. Further analysis indicated that TLR9 expression was obviously associated with other stem cell markers and drug transporters. Of which, beta-catenin, was found to be positively related to TLR9 expression. Thus, it is possible that TLR9 induce the expression of those molecules, finally leads to the CSC proliferation and drug resistance. All these results provide evidences that TLR9 is a CSC phenotype maintainer in lung cancer.

CONCLUSIONS: TLR9 is necessary for maintenance of lung CSC phenotype. It might be a functional marker for lung CSCs.

CLINICAL IMPLICATIONS: Our data suggested that TLR9 might be a cancer stem cell marker and thus provide a potential therapeutic target for treatment of lung cancer.

DISCLOSURE: The following authors have nothing to disclose: Fengying Wu, Shan Shan, Yang Han, Tao Ren

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