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Monitoring Breast Cancer Growth and Metastatic Colony Formation in Mice using Bioluminescence
Published on: November 5, 2021
Interleukin-34 contributes to poor prognosis in triple-negative breast cancer
Nabeel Kajihara1, Fumihito Kitagawa1, Takuto Kobayashi1
1Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Sapporo, 060-0815, Japan.
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.
Insights
Triple-negative breast cancer (TNBC) has poor prognosis due to lack of targets. Interleukin-34 (IL-34) is highly expressed in TNBC, correlating with lower survival and suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies, necessitating novel therapeutic strategies.
- Interleukin-34 (IL-34), a cytokine implicated in inflammation and tumorigenesis, has been linked to poor prognosis in several cancers.
Purpose of the Study:
- To investigate the role of IL-34 in the progression and prognosis of TNBC.
- To evaluate IL-34 as a potential therapeutic target for TNBC.
Main Methods:
- Analysis of IL-34 expression in human TNBC clinical samples.
- Correlation of IL-34 levels with patient survival rates.
- Multivariate analysis to assess IL-34's independent prognostic value.
- Evaluation of IL-34's role in a murine TNBC model.
Main Results:
- IL-34 was significantly upregulated in TNBC tissues.
- High IL-34 expression in TNBC patients was associated with poorer survival outcomes.
- IL-34 independently predicted prognosis in TNBC.
- In a mouse model, IL-34 deficiency in tumor cells reduced tumor growth and enhanced macrophage-mediated inflammatory responses.
Conclusions:
- Tumor-derived IL-34 promotes TNBC growth by creating a pro-tumorigenic microenvironment.
- IL-34 represents a novel pathological factor in TNBC.
- IL-34 holds potential as a therapeutic target for triple-negative breast cancer.

