炎症性肿瘤微环境（TME）是肿瘤促进过程的关键驱动因素。肿瘤相关巨噬细胞是 TME 中的主要免疫细胞类型之一，其密度增加与前列腺癌的不良预后相关。在这里，我们研究了促炎性（M1）和免疫抑制性（M2）巨噬细胞对前列腺癌谱系可塑性的影响。我们的研究结果表明，M1 巨噬细胞分泌的因子上调与干性相关的基因，同时下调与前列腺癌细胞中雄激素反应相关的基因。 M1 巨噬细胞分泌的因子刺激了癌症干细胞 (CSC) 可塑性标志物 NANOG、KLF4、SOX2、OCT4 和 CD44 的表达。此外，在用 M1 巨噬细胞分泌因子处理的 LNCaP 细胞中，观察到 AR 及其靶基因 PSA 受到抑制。使用 IKK16 抑制剂抑制 NFκB 信号传导导致 NANOG、SOX2、CD44 和 CSC 可塑性下调。我们的研究强调，M1 巨噬细胞分泌的因子通过 NFκB 信号通路上调 CSC 可塑性标志物的表达来驱动前列腺癌细胞可塑性。© 2024 作者。经泰勒许可出版

The inflammatory tumor microenvironment (TME) is a key driver for tumor-promoting processes. Tumor-associated macrophages are one of the main immune cell types in the TME and their increased density is related to poor prognosis in prostate cancer. Here, we investigated the influence of pro-inflammatory (M1) and immunosuppressive (M2) macrophages on prostate cancer lineage plasticity. Our findings reveal that M1 macrophage secreted factors upregulate genes related to stemness while downregulating genes associated with androgen response in prostate cancer cells. The expression of cancer stem cell (CSC) plasticity markers NANOG, KLF4, SOX2, OCT4, and CD44 was stimulated by the secreted factors from M1 macrophages. Moreover, AR and its target gene PSA were observed to be suppressed in LNCaP cells treated with secreted factors from M1 macrophages. Inhibition of NFκB signaling using the IKK16 inhibitor resulted in downregulation of NANOG, SOX2, and CD44 and CSC plasticity. Our study highlights that the secreted factors from M1 macrophages drive prostate cancer cell plasticity by upregulating the expression of CSC plasticity markers through NFκB signaling pathway.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.