Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line

IF 4.3 3区生物学 Human Cell Pub Date : 2024-04-03 DOI:10.1007/s13577-024-01054-1

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Abstract

Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.

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新型侵袭性人类皮肤鳞状细胞癌细胞系 HCB-541 的建立与分子特征描述

摘要皮肤鳞状细胞癌（cSCC）是一种常见的皮肤癌，可导致严重的发病率，但通常治疗效果良好，很少发生转移。然而，由于缺乏商业化的 cSCC 细胞系，阻碍了我们对这种疾病的了解。本研究旨在建立一种新的转移性 cSCC 细胞系，并描述其特征，该细胞系来自一名巴西患者。研究人员从一名转移性 cSCC 患者身上提取了肿瘤活检组织，经过数次传代后将其永生化并命名为 HCB-541。对细胞角蛋白表达谱、核型改变、突变分析、mRNA和蛋白质差异表达、异种移植模型的致瘤能力以及药物敏感性进行了分析。在异种移植小鼠模型中，HCB-541细胞系的倍增时间在20至30小时之间，具有很强的致瘤能力。HCB-541细胞系表现出低二倍体和低四倍体。我们在肿瘤和细胞系中发现了TP53 p.（Arg248Leu）、HRAS（Gln61His）和TERT启动子（C228T）的致病突变以及高水平的微卫星不稳定性（MSI-H）。与 HACAT 对照细胞相比，我们观察到 37 个癌症相关基因有差异表达。HCB-541细胞的表皮生长因子受体（EGFR）、AXL、Tie、FGFR和ROR2的磷酸化水平较高，对顺铂、卡铂和EGFR抑制剂的敏感性也较高。我们的研究成功建立了 HCB-541 这一新的 cSCC 细胞系，它可以作为了解转移性皮肤癌的生物学和治疗的重要生物学模型。

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来源期刊

Human Cell 生物-细胞生物学

CiteScore

6.60

自引率

2.30%

发文量

176

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.