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IL-8 regulates the stemness properties of cancer stem cells in the small-cell lung cancer cell line H446

Authors Jin F, Miao Y, Xu P, Qiu X

Received 6 January 2018

Accepted for publication 25 June 2018

Published 11 September 2018 Volume 2018:11 Pages 5723—5731

DOI https://doi.org/10.2147/OTT.S161760

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Justinn Cochran

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Fang Jin,1,2,* Yajing Miao,3,* Pengyu Xu,1 Xiaofei Qiu1

1Department of Pathology, Tianjin Medical University, Tianjin, China; 2Respiratory Department, Tianjin Medical University General Hospital, Tianjin, China; 3Research Center for Basic Medical Science, Tianjin Medical University, Tianjin, China

*These authors contributed equally to this work

Purpose: Cancer stem cells (CSCs) are a small population of cancer cells located within a tumor that are highly tumorigenic, capable of tumor initiation, and resistant to cancer therapies. We identified the potential genes involved in regulating stemness properties and investigated the mechanisms in small-cell lung cancer (SCLC).
Materials and methods: Whole transcriptome sequencing technology was used to screen the potential genes involved in regulating stemness properties from SCLC-SCs (uPAR+) and differentiated cells (uPAR-) in the H446 cell line. The selected genes were validated by quantitative reverse transcription PCR and ELISAs. The effect of IL-8 on stemness of sphere-forming cells was determined through tumor sphere formation, wound healing migration, and in vivo tumorigenesis assays.
Results: In our study, uPAR+ and uPAR- cells showed different gene expression profiles. IL-8 was upregulated in SCLC sphere-forming cells. Blocking IL-8 expression with siRNA led to loss of stemness, including the self-renewal capability, migration, expression of stemness-related genes, and in vivo tumorigenicity, in sphere-forming cells. Consistently, exogenously added IL-8 enhanced stemness properties in parental cells.
Conclusion: IL-8 was upregulated in SCLC sphere-forming cells, and critical for the acquisition and/or maintenance of the stemness features in the SCLC cell line H446. Our results suggest that blocking IL-8 signaling may provide a novel therapeutic approach for targeting SCLC-SCs and improve treatment and outcomes in SCLC.

Keywords: small-cell lung cancer, cancer stem cells, tumor sphere, IL-8, uPAR, stemness

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