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集落刺激因子 1（CSF1）的表达升高诱导上皮细胞-Gp130 依赖的前列腺上皮内瘤形成。

Elevated expression of the colony-stimulating factor 1 (CSF1) induces prostatic intraepithelial neoplasia dependent of epithelial-Gp130.

机构信息

Department of Urology, University of Washington, Seattle, WA, 98109, USA.

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.

出版信息

Oncogene. 2022 Feb;41(9):1309-1323. doi: 10.1038/s41388-021-02169-7. Epub 2022 Jan 8.

DOI:10.1038/s41388-021-02169-7
PMID:34999736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8882147/
Abstract

Macrophages are increased in human benign prostatic hyperplasia and prostate cancer. We generate a Pb-Csf1 mouse model with prostate-specific overexpression of macrophage colony-stimulating factor (M-Csf/Csf1). Csf1 overexpression promotes immune cell infiltration into the prostate, modulates the macrophage polarity in a lobe-specific manner, and induces senescence and low-grade prostatic intraepithelial neoplasia (PIN). The Pb-Csf1 prostate luminal cells exhibit increased stem cell features and undergo an epithelial-to-mesenchymal transition. Human prostate cancer patients with high CSF-1 expression display similar transcriptional alterations with the Pb-Csf1 model. P53 knockout alleviates senescence but fails to progress PIN lesions. Ablating epithelial Gp130 but not Il1r1 substantially blocks PIN lesion formation. The androgen receptor (AR) is downregulated in Pb-Csf1 mice. ChIP-Seq analysis reveals altered AR binding in 2482 genes although there is no significant widespread change in global AR transcriptional activity. Collectively, our study demonstrates that increased macrophage infiltration causes PIN formation but fails to transform prostate cells.

摘要

巨噬细胞在人类良性前列腺增生和前列腺癌中增加。我们生成了一种前列腺特异性过表达巨噬细胞集落刺激因子 (M-Csf/Csf1) 的 Pb-Csf1 小鼠模型。Csf1 的过表达促进免疫细胞浸润前列腺，以叶特异性方式调节巨噬细胞极性，并诱导衰老和低级别前列腺上皮内瘤变 (PIN)。Pb-Csf1 前列腺腔细胞表现出增加的干细胞特征，并经历上皮-间充质转化。具有高 CSF-1 表达的人类前列腺癌患者显示出与 Pb-Csf1 模型相似的转录改变。P53 基因敲除减轻衰老但未能进展为 PIN 病变。上皮细胞 Gp130 的缺失而非 Il1r1 的缺失可显著阻止 PIN 病变的形成。AR 在 Pb-Csf1 小鼠中下调。ChIP-Seq 分析显示，尽管在全局 AR 转录活性中没有明显的广泛变化，但在 2482 个基因中存在改变的 AR 结合。总之，我们的研究表明，巨噬细胞浸润增加导致 PIN 形成，但未能转化前列腺细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f94a/8882147/18a8be60fae9/nihms-1766779-f0007.jpg
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Nat Commun. 2020 Sep 9;11(1):4498. doi: 10.1038/s41467-020-18313-y.
2
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J Immunol. 2018 Nov 15;201(10):2923-2933. doi: 10.4049/jimmunol.1800352. Epub 2018 Oct 10.
3
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Cancer Immunol Immunother. 2023 Oct;72(10):3349-3362. doi: 10.1007/s00262-023-03496-2. Epub 2023 Jul 28.
4
Androgen-regulated stromal complement component 7 (C7) suppresses prostate cancer growth.雄激素调节的基质补体成分 7（C7）抑制前列腺癌生长。
Oncogene. 2023 Aug;42(32):2428-2438. doi: 10.1038/s41388-023-02759-7. Epub 2023 Jul 3.
5
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6
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