Inflammatory macrophage derived TNFα downregulates estrogen receptor α via FOXO3a inactivation in human breast cancer cells
作者： Frida Björk Gunnarsdóttir , Catharina Hagerling , Caroline Bergenfelz , Meliha Mehmeti , Eva Källberg
DOI: 10.1016/J.YEXCR.2020.111932
关键词:
摘要: Patients with estrogen receptor α positive (ERα+) breast cancer can respond to endocrine therapy, but treatment resistance is common and associated downregulation of ERα expression in the dormant residual cells. Here we show, using long-term NSG xenograft models human primary monocytes, vitro cell cultures tumors from patients, that macrophage derived tumor necrosis factor alpha (TNFα) downregulates cells via inactivation transcription Forkhead box O 3a (FOXO3a). Moreover, presence macrophages was negativity, worse prognosis patients ERα+ tumors. We propose pro-inflammatory macrophages, despite being tumoricidal, may have direct effects on progression patients. Our findings suggest TNFα antagonists should be evaluated for cancer.
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