癌症研究
间质细胞
白血病抑制因子
信号转导
肿瘤微环境
白血病抑制因子受体
生物
细胞生物学
免疫系统
化学
免疫学
细胞因子
白细胞介素6
作者
Ke Hung Tsui,Chien‐Liang Liu,Hsiu-Lien Yeh,Mingkun Liu,Chien‐Hsiu Li,Wei‐Hao Chen,Kuo-Ching Jiang,Han‐Ru Li,Phan Vu Thuy Dung,Michael Hsiao,Wassim Abou‐Kheir,Yen‐Nien Liu
出处
期刊:iScience
[Elsevier]
日期:2024-07-20
卷期号:27 (8): 110562-110562
标识
DOI:10.1016/j.isci.2024.110562
摘要
The interaction between prostate cancer (PCa) cells and prostate stromal cells fosters an immunosuppressive tumor microenvironment (TME) that promotes tumor growth and immune evasion. However, the specific signaling pathways involved remain unclear. We identified a key mechanism involving the CXCL5/CXCR2 and LIF/LIFR pathways, which create a feedforward loop that enhances neuroendocrine differentiation (NED) in PCa cells and upregulates WNT1-inducible signaling pathway protein 1 (WISP1) in both cell types. WISP1 upregulation is essential for inducing immune checkpoints and immunosuppressive cytokines via LIF/LIFR signaling and STAT3 phosphorylation. This process leads to increased neuroendocrine markers, immune checkpoints, cell proliferation, and migration. Notably, WISP1 levels in patient sera correlate with PCa progression, suggesting its potential as a biomarker. Our findings elucidate the mechanisms by which reciprocal communication between PCa cells and stromal cells contributes to the formation of an immunosuppressive TME, driving the malignant progression of PCa and highlighting potential targets for therapeutic intervention.
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