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间充质细胞在胆管癌中的作用。

The role of mesenchymal cells in cholangiocarcinoma.

作者信息

Sueca-Comes Mireia, Rusu Elena Cristina, Ashworth Jennifer C, Collier Pamela, Probert Catherine, Ritchie Alison, Meakin Marian, Mongan Nigel P, Egbuniwe Isioma U, Andersen Jesper Bøje, Bates David O, Grabowska Anna M

机构信息

Translational Medical Science, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, UK.

Institute of Integrative Systems Biology (I2Sysbio), University of Valencia and Consejo Superior de Investigaciones Científicas (CSIC), 46980 Valencia, Spain.

出版信息

Dis Model Mech. 2024 Dec 1;17(12). doi: 10.1242/dmm.050716. Epub 2024 Dec 13.

DOI:10.1242/dmm.050716
PMID:39492622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11655028/
Abstract

The tumour microenvironment (TME) significantly influences tumour formation and progression through dynamic interactions. Cholangiocarcinoma (CCA), a highly desmoplastic tumour, lacks early diagnostic biomarkers and has limited effective treatments owing to incomplete understanding of its molecular pathogenesis. Investigating the role of the TME in CCA progression could lead to better therapies. RNA sequencing was performed on seven CCA patient-derived xenografts (PDXs) and their corresponding patient samples. Differential expression analysis was conducted, and Qiagen Ingenuity Pathway Analysis was used to predict dysregulated pathways and upstream regulators. PDX- and cell line-derived spheroids, with and without immortalised mesenchymal stem cells, were grown and analysed for morphology, growth and viability. Histological analysis confirmed biliary phenotypes. RNA sequencing indicated upregulation of extracellular matrix-receptor interaction and PI3K-AKT pathways in the presence of mesenchymal cells, with several genes linked to poor survival. Mesenchymal cells restored the activity of inhibited cancer-associated kinases. Thus, adding mesenchymal cells to CCA spheroid models restored key paracrine signalling pathways lost in PDXs, enhancing tumour growth and viability. These findings highlight the importance of including stromal components in cancer models to improve pre-clinical studies.

摘要

肿瘤微环境（TME）通过动态相互作用显著影响肿瘤的形成和进展。胆管癌（CCA）是一种高度促结缔组织增生性肿瘤，由于对其分子发病机制的认识不全面，缺乏早期诊断生物标志物且有效治疗方法有限。研究TME在CCA进展中的作用可能会带来更好的治疗方法。对七个源自CCA患者的异种移植瘤（PDX）及其相应的患者样本进行了RNA测序。进行了差异表达分析，并使用Qiagen Ingenuity通路分析来预测失调的通路和上游调节因子。培养了带有和不带有永生化间充质干细胞的源自PDX和细胞系的球体，并对其形态、生长和活力进行了分析。组织学分析证实了胆管表型。RNA测序表明，在间充质细胞存在的情况下，细胞外基质-受体相互作用和PI3K-AKT通路上调，有几个基因与不良生存相关。间充质细胞恢复了受抑制的癌症相关激酶的活性。因此，将间充质细胞添加到CCA球体模型中可恢复PDX中丧失的关键旁分泌信号通路，增强肿瘤生长和活力。这些发现突出了在癌症模型中纳入基质成分以改善临床前研究的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/6441d52f6289/dmm-17-050716-g8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/d3e8f6aae69b/dmm-17-050716-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/29e2940ae901/dmm-17-050716-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/f1961e8e67f4/dmm-17-050716-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/d58bb1d39e17/dmm-17-050716-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/d8d6387af8f1/dmm-17-050716-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/38b0175cd84a/dmm-17-050716-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/cdbcf89a9d31/dmm-17-050716-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/6441d52f6289/dmm-17-050716-g8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/d3e8f6aae69b/dmm-17-050716-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/29e2940ae901/dmm-17-050716-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/f1961e8e67f4/dmm-17-050716-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/d58bb1d39e17/dmm-17-050716-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/d8d6387af8f1/dmm-17-050716-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/38b0175cd84a/dmm-17-050716-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/cdbcf89a9d31/dmm-17-050716-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab5/11655028/6441d52f6289/dmm-17-050716-g8.jpg

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In Vitro Model. 2023;2(3-4):99-111. doi: 10.1007/s44164-023-00048-x. Epub 2023 May 9.
2
ROR1-AS1 might promote in vivo and in vitro proliferation and invasion of cholangiocarcinoma cells.ROR1-AS1 可能促进胆管癌细胞的体内和体外增殖和侵袭。
BMC Cancer. 2023 Sep 28;23(1):912. doi: 10.1186/s12885-023-11412-1.
3
Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments.
Front Cell Dev Biol. 2025 Jan 9;12:1536854. doi: 10.3389/fcell.2024.1536854. eCollection 2024.
肿瘤进展和免疫逃逸中的细胞外基质重塑：从机制到治疗。
Mol Cancer. 2023 Mar 11;22(1):48. doi: 10.1186/s12943-023-01744-8.
4
Implications of Three-Dimensional Cell Culture in Cancer Therapeutic Research.三维细胞培养在癌症治疗研究中的意义
Front Oncol. 2022 May 12;12:891673. doi: 10.3389/fonc.2022.891673. eCollection 2022.
5
Single-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma.单细胞转录组分析提示肝内胆管癌存在两种分子亚型。
Nat Commun. 2022 Mar 28;13(1):1642. doi: 10.1038/s41467-022-29164-0.
6
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7
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