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BPIFB1 通过诱导巨噬细胞 M2 样极化促进激素受体阳性乳腺癌的转移。

BPIFB1 promotes metastasis of hormone receptor-positive breast cancer via inducing macrophage M2-like polarization.

机构信息

Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of General Surgery, Daqing Oilfield General Hospital, Daqing, China.

出版信息

Cancer Sci. 2023 Nov;114(11):4157-4171. doi: 10.1111/cas.15957. Epub 2023 Sep 13.

Abstract

Metastasis is an important factor affecting the prognosis of hormone receptor-positive breast cancer (BC). However, the molecular basis for migration and invasion of tumor cells remains poorly understood. Here, we identify that bactericidal/permeability-increasing-fold-containing family B member 1 (BPIFB1), which plays an important role in innate immunity, is significantly elevated in breast cancer and associated with lymph node metastasis. High expression of BPIFB1 and its coding mRNA are significantly associated with poor prognosis of hormone receptor-positive BC. Using enrichment analysis and constructing immune infiltration evaluation, we predict the potential ability of BPIFB1 to promote macrophage M2 polarization. Finally, we demonstrate that BPIFB1 promotes the metastasis of hormone receptor-positive BC by stimulating the M2-like polarization of macrophages via the establishment of BC tumor cells/THP1 co-culture system, qPCR, Transwell assay, and animal experiments. To our knowledge, this is the first report on the role of BPIFB1 as a tumor promoter by activating the macrophage M2 polarization in hormone receptor-positive breast carcinoma. Together, these results provide novel insights into the mechanism of BPIFB1 in BC.

摘要

转移是影响激素受体阳性乳腺癌(BC)预后的重要因素。然而,肿瘤细胞迁移和侵袭的分子基础仍知之甚少。在这里,我们发现杀菌/通透性增加蛋白家族 B 成员 1(BPIFB1)在先天免疫中发挥重要作用,在乳腺癌中显著升高,并与淋巴结转移相关。BPIFB1 高表达及其编码 mRNA 与激素受体阳性 BC 的预后不良显著相关。通过富集分析和构建免疫浸润评估,我们预测了 BPIFB1 促进巨噬细胞 M2 极化的潜在能力。最后,我们通过建立 BC 肿瘤细胞/THP1 共培养系统、qPCR、Transwell 测定和动物实验,证明 BPIFB1 通过刺激巨噬细胞 M2 样极化促进激素受体阳性 BC 的转移。据我们所知,这是首次报道 BPIFB1 通过激活激素受体阳性乳腺癌中的巨噬细胞 M2 极化来促进肿瘤的发生。总之,这些结果为 BPIFB1 在 BC 中的作用机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1108/10637056/d85d1d28351e/CAS-114-4157-g004.jpg

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