表达 cMYB 的人唾液腺样囊性癌细胞系 (UM-HACC-14、UM-HACC-6) 和匹配的患者来源异种移植模型 (UM-PDX-HACC-14) 的建立和表征。
Establishment and characterization of cMYB-expressing human salivary adenoid cystic carcinoma cell lines (UM-HACC-14, UM-HACC-6) and matching patient-derived xenograft model (UM-PDX-HACC-14).
发表日期:2024 Jun 11
作者:
Kristy A Warner, Alexandra E Herzog, Sosuke Sahara, Felipe Nör, Rogerio M Castilho, Hakan Demirci, Douglas B Chepeha, Peter J Polverini, Jacques E Nör
来源:
Disease Models & Mechanisms
摘要:
真正的人类腺样囊性癌 (ACC) 细胞系的可用性有限,阻碍了对该疾病生物学基础机制的理解以及安全有效疗法的开发。外科人类 ACC 标本(UM-HACC-6、UM-HACC-14) )被解离成单细胞悬浮液并在纤连蛋白包被的烧瓶中培养。或者,将肿瘤碎片皮下移植到雌性免疫缺陷 (SCID) 小鼠中,以建立患者来源的异种移植肿瘤 (PDX;UM-PDX-HACC-14)。两种 ACC 细胞系均显示单层连续生长超过 100 代。总 RNA-Seq、RT-PCR 和 FISH 分析显示,两者均为 MYB-NFIB 融合阴性。蛋白质印迹显示 E-钙粘蛋白、PCNA、p63、磷酸-c-MYB 和 NFIB 的传代依赖性表达。当原位注射到小鼠颌下腺中时,UM-HACC-14 和 UM-HACC-6 细胞均表现出致瘤潜力。UM-HACC-14、患者匹配的 UM-PDX-HACC-14 和 UM-HACC-6 细胞系列是新的、经过验证的 ACC 临床前模型,非常适合机械和发育治疗研究。版权所有 © 2024 Elsevier Inc. 保留所有权利。
Limited availability of authentic human adenoid cystic carcinoma (ACC) cell lines has hindered progress in understanding mechanisms underpinning the biology of this disease and the development of safe and effective therapies.Surgical human ACC specimens (UM-HACC-6, UM-HACC-14) were dissociated into single cell suspensions and cultured in fibronectin-coated flasks. Alternatively, tumor fragments were transplanted subcutaneously into female immunodeficient (SCID) mice to establish patient-derived xenograft tumors (PDX; UM-PDX-HACC-14).Both ACC cell lines showed continuous growth in monolayers for over 100 passages. Total RNA-Seq, RT-PCR, and FISH analysis revealed that both are MYB-NFIB fusion negative. Western blots revealed passage-dependent expression of E-Cadherin, PCNA, p63, phospho-c-MYB, and NFIB. Both, UM-HACC-14 and UM-HACC-6 cells exhibited tumorigenic potential when injected orthotopically into mouse submandibular glands.UM-HACC-14, patient-matching UM-PDX-HACC-14, and the UM-HACC-6 cell line are new, authenticated preclinical models of ACC that are well suited for mechanistic and developmental therapeutics studies.Copyright © 2024 Elsevier Inc. All rights reserved.