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

Abstract 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 descr...

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Autores principales: 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
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2020
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602020000100211
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spelling oai:scielo:S0716-976020200001002112020-06-25Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumorGarcía,PatriciaBizama,CarolinaRosa,LorenaEspinoza,Jaime A.Weber,HelgaCerda-Infante,JavierSánchez,MarianelaMontecinos,Viviana P.Lorenzo-Bermejo,JustoBoekstegers,FelixDávila-López,MarcelaAlfaro,FranciscaLeiva-Acevedo,ClaudiaParra,ZashaRomero,DiegoKato,SumieLeal,PamelaLagos,MarcelaRoa,Juan Carlos Gallbladder cancer Cancer cell lines Ascites Native American ancestry Gene expression profile Abstract 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.53 20202020-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602020000100211en10.1186/s40659-020-00282-7
institution Scielo Chile
collection Scielo Chile
language English
topic Gallbladder cancer
Cancer cell lines
Ascites
Native American ancestry
Gene expression profile
spellingShingle Gallbladder cancer
Cancer cell lines
Ascites
Native American ancestry
Gene expression profile
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
Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor
description Abstract 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.
author 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
author_facet 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
author_sort García,Patricia
title Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor
title_short Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor
title_full Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor
title_fullStr Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor
title_full_unstemmed Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor
title_sort functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor
publisher Sociedad de Biología de Chile
publishDate 2020
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602020000100211
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