Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor

Biological research: BR

article

García, Patricia¹  Boekstegers, Felix²  Dávila-López, Marcela³  Alfaro, Francisca¹  Leiva-Acevedo, Claudia¹  Parra, Zasha⁴  Romero, Diego¹  Kato, Sumie⁵  Leal, Pamela⁶  Lagos, Marcela⁷  Roa, Juan Carlos⁸  Bizama, Carolina¹  Rosa, Lorena¹  Espinoza, Jaime A.^1,10  Weber, Helga⁶  Cerda-Infante, Javier^1,11  Sánchez, Marianela^1,12  Montecinos, Viviana P.^1,12  Lorenzo-Bermejo, Justo² 

[1] Department of Pathology, Faculty of Medicine, Pontificia Universidad Católica de Chile;Statistical Genetics Research Group, Institute of Medical Biometry and Informatics, University of Heidelberg;University of Gothenburg;Cytogenetics Laboratory;Division of Obstetrics and Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile;Center of Excellence in Translational Medicine (CEMT) and Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera;Department of Clinical Laboratory, Faculty of Medicine, Pontificia Universidad Católica de Chile;Department of Pathology, Faculty of Medicine, Millennium Institute of Immunology and Immunotherapy, Pontificia Universidad Católica de Chile;Applied Molecular and Cellular Biology PhD Program, Universidad de La Frontera;Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet;Department of Hematology Oncology;Department of Hematology Oncology, Pontificia Universidad Católica de Chile

关键词: Gallbladder cancer;    Cancer cell lines;    Ascites;    Native American ancestry;    Gene expression profile;   

DOI  :  10.1186/s40659-020-00282-7

来源: BioMed Central

【 摘 要 】

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. 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. The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.

【 授权许可】

Unknown