Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor. 2020

Patricia García, and Carolina Bizama, and Lorena Rosa, and Jaime A Espinoza, and Helga Weber, and Javier Cerda-Infante, and Marianela Sánchez, and Viviana P Montecinos, and Justo Lorenzo-Bermejo, and Felix Boekstegers, and Marcela Dávila-López, and Francisca Alfaro, and Claudia Leiva-Acevedo, and Zasha Parra, and Diego Romero, and Sumie Kato, and Pamela Leal, and Marcela Lagos, and Juan Carlos Roa
Department of Pathology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.

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.

UI MeSH Term Description Entries
D007199 Indians, South American Members of indigenous South American populations with pre-colonial contact origins. Amerinds, South American,Indigenous South Americans,American Amerind, South,American Indian, South,American, Indigenous South,Americans, Indigenous South,Amerind, South American,Indian, South American,Indigenous South American,South American Amerind,South American Amerinds,South American Indian,South American Indians,South American, Indigenous,South Americans, Indigenous
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D002677 Chile A country in southern South America, bordering the South Pacific Ocean, between Argentina and Peru.
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D003841 Deoxycytidine A nucleoside component of DNA composed of CYTOSINE and DEOXYRIBOSE. Cytosine Deoxyribonucleoside,Cytosine Deoxyriboside,Deoxyribonucleoside, Cytosine,Deoxyriboside, Cytosine
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005706 Gallbladder Neoplasms Tumors or cancer of the gallbladder. Cancer of Gallbladder,Gallbladder Cancer,Cancer of the Gallbladder,Gall Bladder Cancer,Neoplasms, Gallbladder,Bladder Cancer, Gall,Bladder Cancers, Gall,Cancer, Gall Bladder,Cancer, Gallbladder,Cancers, Gall Bladder,Cancers, Gallbladder,Gall Bladder Cancers,Gallbladder Cancers,Gallbladder Neoplasm,Neoplasm, Gallbladder
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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