Establishment and characteristic analysis of a novel patient derived cell line of intrahepatic cholangiocarcinoma.

IF 6 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-10-15 DOI:10.1186/s12935-025-03989-3

Shuangshuang Dou, Minghui Gao, Quanwei Li, Mengyin Chai, Buxin Kou, Xiaoni Liu

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引用次数: 0

Abstract

Background: Intrahepatic cholangiocarcinoma (ICC) is a primary malignant tumor of the liver, second only to hepatocellular carcinoma. The scarcity of appropriate cell lines has impeded ICC-related research. This study aims to establish a novel patient-derived ICC cell line and systematically evaluate its biological characteristics, thereby providing a valuable cellular tool for ICC research.

Methods: A cell line named LPHC-6 of ICC was established using a patient-derived xenograft (PDX) tumor model. We comprehensively characterized this novel cell line through a series of techniques, including cell morphology observation, short tandem repeat (STR) analysis, karyotype analysis, cell proliferation, cell migration assays, western blot analysis, immunofluorescence staining, flow cytometry, gene mutation detection, spheroid formation assays, drug sensitivity testing, and xenograft tumor formation in nude mice.

Results: LPHC-6 cells exhibited typical characteristics of malignant epithelial cells, demonstrating robust proliferation and migration capabilities. These cells possessed a structurally complex triploid karyotype, which was confirmed to be free from cross-contamination with other human cell lines. Tumor biomarker analysis revealed positive expression of AFP and negative expression of GPC3. Additionally, LPHC-6 cells showed high expression levels of stem cell markers CD133 and CD44. The biliary epithelial cell marker CK19 was positive, whereas the hepatocyte marker Hep Par1 was negative. Genomic analysis identified an exon mutation in TP53, copy number loss in PTEN and RAD51, and copy number gain in NTRK1, PDCD1LG2, and VEGFA. Investigations confirmed that LPHC-6 cells exhibited excellent sphere formation ability and tumorigenic potential. Furthermore, LPHC-6 cells demonstrated sensitivity to Sorafenib, Lenvatinib, 5-fluorouracil, Oxaliplatin and Atezolizumab in both 2D and 3D culture system.

Conclusion: A novel intrahepatic cholangiocarcinoma cell line LPHC-6 has been successfully established, which provides a powerful cell tool for the research related to intrahepatic cholangiocarcinoma.

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一种新型肝内胆管癌患者来源细胞系的建立及特性分析。

背景：肝内胆管癌（ICC）是一种原发性肝脏恶性肿瘤，仅次于肝细胞癌。适当细胞系的缺乏阻碍了icc相关的研究。本研究旨在建立一种新的患者源性ICC细胞系，并系统评价其生物学特性，从而为ICC研究提供有价值的细胞工具。方法：采用患者源性异种移植（PDX）肿瘤模型建立ICC细胞系LPHC-6。我们通过一系列技术，包括细胞形态学观察、短串联重复（STR）分析、核型分析、细胞增殖、细胞迁移试验、western blot分析、免疫荧光染色、流式细胞术、基因突变检测、球体形成试验、药物敏感性试验和裸鼠异种移植肿瘤形成等，全面表征了这一新型细胞系。结果：LPHC-6细胞表现出典型的恶性上皮细胞特征，具有强大的增殖和迁移能力。这些细胞具有结构复杂的三倍体核型，证实与其他人类细胞系没有交叉污染。肿瘤生物标志物分析显示AFP阳性表达，GPC3阴性表达。此外，LPHC-6细胞显示高水平表达干细胞标志物CD133和CD44。胆道上皮细胞标志物CK19呈阳性，而肝细胞标志物Hep Par1呈阴性。基因组分析发现了TP53的外显子突变，PTEN和RAD51的拷贝数丢失，NTRK1、PDCD1LG2和VEGFA的拷贝数增加。研究证实LPHC-6细胞具有优异的成球能力和致瘤潜能。此外，在2D和3D培养系统中，LPHC-6细胞对索拉非尼、Lenvatinib、5-氟尿嘧啶、奥沙利铂和Atezolizumab均表现出敏感性。结论：成功建立了一种新的肝内胆管癌细胞系LPHC-6，为肝内胆管癌的相关研究提供了强有力的细胞工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.