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Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor.
Biological Research ( IF 4.3 ) Pub Date : 2020-04-15 , DOI: 10.1186/s40659-020-00282-7
Patricia García 1 , Carolina Bizama 1 , Lorena Rosa 1, 2 , Jaime A Espinoza 3 , Helga Weber 4 , Javier Cerda-Infante 5 , Marianela Sánchez 6 , Viviana P Montecinos 6 , Justo Lorenzo-Bermejo 7 , Felix Boekstegers 7 , Marcela Dávila-López 8 , Francisca Alfaro 1 , Claudia Leiva-Acevedo 1 , Zasha Parra 9 , Diego Romero 1 , Sumie Kato 10 , Pamela Leal 4 , Marcela Lagos 11 , Juan Carlos Roa 12
Affiliation  

BACKGROUND Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry. RESULTS After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes. RNA sequencing confirmed the increased expression of cytokeratin and mucin genes, and also of TP53 and ERBB2 with some differences among the three cells lines, and revealed a novel exonic mutation in NF1. The PUC-GBC3 clone was the most aggressive according to histopathological features and the tumorigenic capacity in NSG mice. CONCLUSIONS The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.

中文翻译:

从转移性胆囊癌肿瘤衍生的三种新型细胞系的功能和基因组学表征。

背景技术胆囊癌(GBC)是最常见的胆道肿瘤。GBC的发病率显示出很大的地理变异性,在美洲印第安人人群中尤为常见。在智利,GBC是女性癌症相关死亡的第二大原因。我们在这里描述了从智利GBC患者的腹水中衍生出的三种新型细胞系的建立,该患者呈现46%的欧洲人,36%的Mapuche,12%的Aymara和6%的非洲血统。结果在对原代细胞培养物进行了免疫细胞化学染色后,我们通过短串联重复DNA分析和RNA测序以及核型,倍增时间,化学敏感性,体外迁移能力和体内致瘤性测定。原代培养细胞显示CK7,CK19,CA 19-9,MUC1和MUC16的高表达,而间皮标志物的阴性表达。三个分离的克隆表现出上皮表型以及异常的染色体结构和数目。RNA测序证实了细胞角蛋白和粘蛋白基因以及TP53和ERBB2的表达增加,这三个细胞系之间存在一些差异,并揭示了NF1中的新的外显子突变。根据组织病理学特征和NSG小鼠的致瘤能力,PUC-GBC3克隆最具有侵略性。结论从智利的GBC患者建立的第一批细胞系代表了一种用于研究美国原住民血统的GBC的新模型。三个分离的克隆表现出上皮表型以及异常的染色体结构和数目。RNA测序证实了细胞角蛋白和粘蛋白基因以及TP53和ERBB2的表达增加,这三个细胞系之间存在一些差异,并揭示了NF1中的新的外显子突变。根据组织病理学特征和NSG小鼠的致瘤能力,PUC-GBC3克隆最具有侵略性。结论从智利的GBC患者建立的第一批细胞系代表了一种用于研究美国原住民血统的GBC的新模型。三个分离的克隆表现出上皮表型以及异常的染色体结构和数目。RNA测序证实了细胞角蛋白和粘蛋白基因以及TP53和ERBB2的表达增加,这三个细胞系之间存在一些差异,并揭示了NF1中的新的外显子突变。根据组织病理学特征和NSG小鼠的致瘤能力,PUC-GBC3克隆最具有侵略性。结论从智利的GBC患者建立的第一批细胞系代表了一种用于研究美国原住民血统的GBC的新模型。并揭示了NF1的新型外显子突变。根据组织病理学特征和NSG小鼠的致瘤能力,PUC-GBC3克隆最具有侵略性。结论从智利的GBC患者建立的第一批细胞系代表了一种用于研究美国原住民血统的GBC的新模型。并揭示了NF1的新型外显子突变。根据组织病理学特征和NSG小鼠的致瘤能力,PUC-GBC3克隆最具有侵略性。结论从智利的GBC患者建立的第一批细胞系代表了一种用于研究美国原住民血统的GBC的新模型。
更新日期:2020-04-22
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