OncoTargets and Therapy (Sep 2018)
IL-8 regulates the stemness properties of cancer stem cells in the small-cell lung cancer cell line H446
Abstract
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
