Interleukin-34 contributes to poor prognosis in triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is a subtype characterized by the absence of therapeutic targets. It shows rapid progression, higher relapse, and poor prognosis, so the establishment of an effective therapeutic target is required. We focused on interleukin-34 (IL-34) that is a novel cytokine relating to inflammation and tumorigenesis. It has been reported that IL-34 correlates with poor prognosis of various cancers. In this study, we evaluated the relationship of IL-34 and prognosis in TNBC using human clinical information and mice model. We found that IL-34 was highly expressed in TNBC, and the survival rate in TNBC was significantly lower in patients with high IL-34 expression. Furthermore, multivariate analysis revealed that IL-34 independently affects prognosis. In murine TNBC model, IL-34 deficiency in tumor cells decreased in vivo tumor growth and increased inflammatory cytokine production from macrophages. These results suggest that tumor-derived IL-34 creates a favorable environment for TNBC cells. Thus, we showed a novel pathological role of IL-34 in TNBC and the potential of IL-34 as a therapeutic target for it.

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Acknowledgements

This work was supported in part by Japan Agency for Medical Research and Development (AMED; Practical Research for Innovative Cancer Control) (K. Seino). The authors thank Muhammad Baghdadi, Hisataka Sabe, Ari Hashimoto, and Haruka Handa for helpful discussions and advice.

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Authors

Contributions

KS and NK designed the study. NK, FK, and TK performed experiments. All authors analyzed data and discussed the results. NK, RO, and KS contributed to manuscript preparation. All authors approved the final version of this manuscript for publication.

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Correspondence to Ken-ichiro Seino.

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The authors declared no potential conflicts of interest.

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All animal procedures were approved by the Animal Care Committee of Hokkaido University (Approval number: 14-0171).

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Kajihara, N., Kitagawa, F., Kobayashi, T. et al. Interleukin-34 contributes to poor prognosis in triple-negative breast cancer. Breast Cancer (2020). https://doi.org/10.1007/s12282-020-01123-x

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Keywords

  • Interleukin-34
  • Triple-negative breast cancer
  • Breast cancer
  • Therapeutic target
  • 4T1