Interleukin-7 Contributes to the Invasiveness of Prostate Cancer Cells by Promoting Epithelial–Mesenchymal Transition

Min A. Seol, Jin Hee Kim, Keunhee Oh, Gwanghun Kim, Myung Won Seo, Young Kyoung Shin, Ji Hyun Sim, Hyun Mu Shin, Bo Yeon Seo, Dong Sup Lee, Ja Lok Ku, Ilkyu Han, Insoo Kang, Serk In Park, Hang Rae Kim

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Abstract

Precise mechanisms underlying interleukin-7 (IL-7)-mediated tumor invasion remain unclear. Thus, we investigated the role of IL-7 in tumor invasiveness using metastatic prostate cancer PC-3 cell line derivatives, and assessed the potential of IL-7 as a clinical target using a Janus kinase (JAK) inhibitor and an IL-7-blocking antibody. We found that IL-7 stimulated wound-healing migration and invasion of PC-3 cells, increased phosphorylation of signal transducer and activator of transcription 5, Akt, and extracellular signal-regulated kinase. On the other hand, a JAK inhibitor and an IL-7-blocking antibody decreased the invasiveness of PC-3 cells. IL-7 increased tumor sphere formation and expression of epithelial–mesenchymal transition (EMT) markers. Importantly, lentiviral delivery of IL-7Rα to PC-3 cells significantly increased bone metastasis in an experimental murine metastasis model compared to controls. The gene expression profile of human prostate cancer cells from The Cancer Genome Atlas revealed that EMT pathways are strongly associated with prostate cancers that highly express both IL-7 and IL-7Rα. Collectively, these data suggest that IL-7 and/or IL-7Rα are promising targets of inhibiting tumor metastasis.

Original languageEnglish
Article number6917
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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    Seol, M. A., Kim, J. H., Oh, K., Kim, G., Seo, M. W., Shin, Y. K., Sim, J. H., Shin, H. M., Seo, B. Y., Lee, D. S., Ku, J. L., Han, I., Kang, I., Park, S. I., & Kim, H. R. (2019). Interleukin-7 Contributes to the Invasiveness of Prostate Cancer Cells by Promoting Epithelial–Mesenchymal Transition. Scientific reports, 9(1), [6917]. https://doi.org/10.1038/s41598-019-43294-4