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癌相关成纤维细胞表达 FHL2 促进肺腺癌的转移和血管生成。

FHL2 expression by cancer-associated fibroblasts promotes metastasis and angiogenesis in lung adenocarcinoma.

机构信息

Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University Cancer Centre, Lund University, Lund, Sweden.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

出版信息

Int J Cancer. 2025 Jan 15;156(2):431-446. doi: 10.1002/ijc.35174. Epub 2024 Sep 8.

DOI:10.1002/ijc.35174
PMID:39244734
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11578086/
Abstract

Cancer-associated fibroblasts (CAFs) contribute to the progression of lung cancer. Four and a half LIM domain protein-2 (FHL2) is a component of focal adhesion structures. We analyzed the function of FHL2 expressed by CAFs in lung adenocarcinoma. Expression of FHL2 in fibroblast subtypes was investigated using database of single-cell RNA-sequencing of lung cancer tissue. The role of FHL2 in the proliferation and migration of CAFs was assessed. The effects of FHL2 knockout on the migration and invasion of human lung adenocarcinoma cells and tube formation of endothelial cells induced by CAF-conditioned medium (CM) were evaluated. The effect of FHL2 knockout in CAFs on metastasis was determined using a murine orthotopic lung cancer model. The prognostic significance of stromal FHL2 was assessed by immunohistochemistry in human adenocarcinoma specimens. FHL2 is highly expressed in myofibroblasts in cancer tissue. TGF-β1 upregulated FHL2 expression in CAFs and FHL2 knockdown attenuated CAF proliferation. FHL2 knockout reduced CAF induced migration of A110L and H23 human lung adenocarcinoma cell lines, and the induction of tube formation of endothelial cells. FHL2 knockout reduced CAF-induced metastasis of lung adenocarcinomas in an orthotopic model in vivo. The concentration of Osteopontin (OPN) in CM from CAF was downregulated by FHL2 knockout. siRNA silencing and antibody blocking of OPN reduced the pro-migratory effect of CM from CAF on lung cancer cells. In resected lung adenocarcinoma specimens, positive stromal FHL2 expression was significantly associated with higher microvascular density and worse prognosis. In conclusion, FHL2 expression by CAFs enhances the progression of lung adenocarcinoma by promoting angiogenesis and metastasis.

摘要

癌症相关成纤维细胞（CAFs）促进肺癌的进展。四半 LIM 结构域蛋白 2（FHL2）是黏着斑结构的组成部分。我们分析了 CAFs 中 FHL2 表达在肺腺癌中的功能。使用肺癌组织单细胞 RNA 测序数据库研究了 FHL2 在成纤维细胞亚型中的表达。评估了 FHL2 对 CAFs 增殖和迁移的作用。评估了 FHL2 敲除对 CAF 条件培养基（CM）诱导的人肺腺癌细胞迁移和侵袭以及内皮细胞管形成的影响。使用小鼠原位肺癌模型评估了 CAFs 中 FHL2 敲除对转移的影响。通过免疫组化评估了基质 FHL2 在人腺癌标本中的预后意义。FHL2 在癌症组织中的肌成纤维细胞中高表达。TGF-β1 上调 CAFs 中的 FHL2 表达，而 FHL2 敲低则减弱 CAF 的增殖。FHL2 敲除减少了 CAF 诱导的 A110L 和 H23 人肺腺癌细胞系的迁移，以及内皮细胞管形成的诱导。FHL2 敲除减少了 CAF 在体内原位模型中诱导的肺腺癌转移。FHL2 敲除下调了 CM 中骨桥蛋白（OPN）的浓度。siRNA 沉默和 OPN 抗体阻断减少了 CM 对肺癌细胞的促迁移作用。在切除的肺腺癌标本中，阳性基质 FHL2 表达与更高的微血管密度和更差的预后显著相关。总之，CAFs 中 FHL2 的表达通过促进血管生成和转移来增强肺腺癌的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/23e3ff619f69/IJC-156-431-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/42abd7a73086/IJC-156-431-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/396bdf90be01/IJC-156-431-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/60b5ee5069ac/IJC-156-431-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/2c0ea351463c/IJC-156-431-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/dbda485f543f/IJC-156-431-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/23e3ff619f69/IJC-156-431-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/42abd7a73086/IJC-156-431-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/248ee50f9c9d/IJC-156-431-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/396bdf90be01/IJC-156-431-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/60b5ee5069ac/IJC-156-431-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/2c0ea351463c/IJC-156-431-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/dbda485f543f/IJC-156-431-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d0/11578086/23e3ff619f69/IJC-156-431-g003.jpg

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本文引用的文献

1
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2
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J Cell Commun Signal. 2023 Sep;17(3):1023-1038. doi: 10.1007/s12079-023-00754-x. Epub 2023 May 22.
3
Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under Hyperglycemic Conditions In Vitro by Inhibiting NF-κB Signaling.
[上皮-间质转化：肺癌侵袭、转移及耐药的生物学基础与临床前景]
Zhongguo Fei Ai Za Zhi. 2025 Feb 20;28(2):155-164. doi: 10.3779/j.issn.1009-3419.2025.102.07.
4
Promotion Mechanisms of Stromal Cell-Mediated Lung Cancer Development Within Tumor Microenvironment.肿瘤微环境中基质细胞介导肺癌发展的促进机制
Cancer Manag Res. 2025 Feb 11;17:249-266. doi: 10.2147/CMAR.S505549. eCollection 2025.
组织蛋白酶 S 敲低通过抑制 NF-κB 信号通路抑制高糖条件下体外血管内皮炎症、血管生成和补体蛋白活性。
Int J Mol Sci. 2023 Mar 12;24(6):5428. doi: 10.3390/ijms24065428.
4
Fibroblast subsets in non-small cell lung cancer: Associations with survival, mutations, and immune features.非小细胞肺癌中的成纤维细胞亚群：与生存、突变及免疫特征的关联
J Natl Cancer Inst. 2023 Jan 10;115(1):71-82. doi: 10.1093/jnci/djac178.
5
Endothelial GATA5 positively regulates angiogenesis via cathepsin S-mediated Angpt2/Flk1 and MMP2/9 signaling pathways.内皮细胞 GATA5 通过组织蛋白酶 S 介导的 Angpt2/Flk1 和 MMP2/9 信号通路正向调节血管生成。
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6
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7
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