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STAT5 regulation of tumor associated macrophage function in murine models of breast cancer

ABSTRACT: In breast cancer, interactions between tumor cells and surrounding stromal cells, such as macrophages, are critical for tumor growth, progression, and therapeutic response. Recent studies have highlighted the complex nature and heterogeneous populations of macrophages associated with both tumor promoting and tumor inhibiting phenotypes. Identifying the specific signaling pathways that regulate macrophage function within the tumor microenvironment will lead to new approaches that suppress tumor promoting functions while enhancing their anti-tumor functions. We demonstrated STAT5 (signal transducer and activator of transcription 5) is robustly activated in tumor-associated macrophages and that granulocyte-macrophage colony stimulating factor (GM-CSF) is a major cytokine stimulating this pathway. To define impacts of GM-CSF/STAT5 on macrophage function, we used in vitro and in vivo models to demonstrate that STAT5 has a significant role in stimulating expression profiles in macrophages consistent with an anti-tumor, adaptive immune response. Our results also indicate that loss of STAT5 in the myeloid lineage leads to enhanced metastatic disease. These findings reveal that disrupted STAT5 signaling in tumor-associated macrophages supports tumor progression, which suggests STAT5 may regulate anti-tumor macrophage function. Understanding how to enhance the anti-tumor capacity of macrophages will be vital in developing effective treatment strategies for patients with aggressive breast cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE171428 | GEO | 2021/11/17

REPOSITORIES: GEO

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