Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor
García, Patricia; Bizama, Carolina; Rosa, Lorena; Espinoza, Jaime A; Weber, Helga; Cerda-Infante, Javier; Sánchez, Marianela; Montecinos, Viviana P; Lorenzo-Bermejo, Justo; Boekstegers, Felix; Dávila-López, Marcela; Alfaro, Francisca; Leiva-Acevedo, Claudia; Parra, Zasha; Romero, Diego; Kato, Sumie; Leal, Pamela; Lagos, Marcela; Roa, Juan Carlos.
Biol. Res
; 53: 13, 2020. tab, graf
Artigo
em Inglês
| LILACS | ID: biblio-1100919
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.Assuntos
Humanos Animais Masculino Pessoa de Meia-Idade Antígenos Glicosídicos Associados a Tumores/genética Indígenas Sul-Americanos/genética Neoplasias da Vesícula Biliar/genética Líquido Ascítico/metabolismo Células Tumorais Cultivadas Testes de Carcinogenicidade Chile Impressões Digitais de DNA Proteína Supressora de Tumor p53/genética Cisplatino/farmacologia Camundongos Endogâmicos NOD Células Clonais/efeitos dos fármacos Células Clonais/metabolismo Análise de Sequência de RNA Receptor ErbB-2/genética Genes erbB-2/genética Perfilação da Expressão Gênica Linhagem Celular Tumoral/efeitos dos fármacos Linhagem Celular Tumoral/metabolismo Desoxicitidina/análogos & derivados Desoxicitidina/farmacologia Células Epiteliais/metabolismo Queratina-19/genética Queratina-7/genética Carcinogênese/genética Neoplasias da Vesícula Biliar/metabolismo Antineoplásicos/farmacologia
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