Establishment and characterization of a new intrahepatic cholangiocarcinoma cell line resistant to gemcitabine
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA477325 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Intrahepatic cholangiocarcinoma (ICC) is one of the most lethal liver cancers. The late diagnosis as well as the resistance to chemotherapy concurred to the scarce outfit of this malignancy. Even the improvement of the knowledge and, as consequence, of the broad spectrum of alternative therapies available (i.e. targeted, immune checkpoint inhibitors), the survival and the quality of life remain poor. The phenomenon of resistance is not still clear. Here, we established one gemcitabine, GEM, (the standard therapy in ICC) resistant cell line, named MTCHC01R1.5, obtained by a gradual exposure to GEM for 9 months (up to 1.5 µM) of the sensible counterpart MT-CHC01. We biologically and molecularly characterized this cell line comparing its behavior with its parental cell line. The drug resistance is irreversible, even if cells are treated with high doses of GEM. They grew slowly, both in vitro and in vivo, and no differences are highlighted in terms of migration and invasion. GEM resistance promoted a multi drug resistance development, but the drug prediction analysis showed that paclitaxel and doxycycline could overcome GEM resistance, as confirmed by cell viability assay. There is a global enrichment of up-regulated genes involved in the regulation of cell cycle and in DNA related process. The down-regulated genes are involved in response to stimuli, and xenobiotic metabolism, and angiogenesis. A deregulation of more than 20 genes related to drug resistance and epithelial to mesenchymal transition (EMT) was found. The trend in expression of 9 genes related to resistance is confirmed in a primary cell culture. In conclusion, we characterized a new Italian GEM resistance ICC model which could be exploited either to study the mechanism of resistance or to explore new therapies.
2019-05-30 | GSE116118 | GEO
Project description:Intrahepatic cholangiocarcinoma (ICC) is one of the most lethal liver cancers. Late diagnosis and chemotherapy resistance contribute to the scarce outfit and poor survival. Resistance mechanisms are still poorly understood. Here, we established a Gemcitabine (GEM) resistant model, the MT-CHC01R1.5 cell line, obtained by a GEM gradual exposure (up to 1.5 µM) of the sensitive counterpart, MT-CHC01. GEM resistance was irreversible, even at high doses. The in vitro and in vivo growth was slower than MT-CHC01, and no differences were highlighted in terms of migration and invasion. Drug prediction analysis suggested that Paclitaxel and Doxycycline might overcome GEM resistance. Indeed, in vitro MT-CHC01R1.5 growth was reduced by Paclitaxel and Doxycycline. Importantly, Doxycycline pretreatment at very low doses restored GEM sensitivity. To assess molecular mechanisms underlying the acquisition of GEM resistance, a detailed analysis of the transcriptome in MT-CHC01R1.5 cells versus the corresponding parental counterpart was performed. Transcriptomic analysis showed that most up-regulated genes were involved in cell cycle regulation and in the DNA related process, while most down-regulated genes were involved in the response to stimuli, xenobiotic metabolism, and angiogenesis. Furthermore, additional panels of drug resistance and epithelial to mesenchymal transition genes (n = 168) were tested by qRT-PCR and the expression of 20 genes was affected. Next, based on a comparison between qRT-PCR and microarray data, a list of up-regulated genes in MT-CHC01R1.5 was selected and further confirmed in a primary cell culture obtained from an ICC patient resistant to GEM. In conclusion, we characterized a new GEM resistance ICC model that could be exploited either to study alternative mechanisms of resistance or to explore new therapies.
| S-EPMC6520787 | biostudies-literature
Project description:We report the gene expression profiles of bulk tumor tissues of intrahepatic cholangiocarcinoma
2020-12-30 | GSE162396 | GEO
Project description:Homo sapiens strain:Intrahepatic cholangiocarcinoma Exome
| PRJNA207681 | ENA
Project description:A \"Cartes d'Identite des Tumeurs\" (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net). This serie showed the heterogeneity of tumor microenvironment across intrahepatic cholangiocarcinoma.
2019-12-28 | E-MTAB-6389 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE32879: Integrative Transcriptomic Profiling reveals Hepatic Stem-like Phenotype and Interplay of EMT and miR-200c in Intrahepatic Cholangiocarcinoma [mRNA] GSE32957: Integrative Transcriptomic Profiling reveals Hepatic Stem-like Phenotype and Interplay of EMT and miR-200c in Intrahepatic Cholangiocarcinoma [miRNA] Refer to individual Series
2012-09-28 | E-GEOD-32958 | biostudies-arrayexpress
Project description:Gene expression signatures for Intrahepatic cholangiocarcinoma
| PRJNA752353 | ENA
Project description:We generated 100 M of high-quality sequencing reads (~10 M per sample) and catalogued the expression profiles of 1643 microRNA in each sample. The analysis showed differences of microRNAs between intrahepatic cholangiocarcinoma and normal bile duct tissues.
2019-12-10 | GSE93366 | GEO
Project description:The experiment was designed to display differential gene expression profiling in three human intrahepatic cholangiocarcinoma (ICC) cells upon knockdow of LKB1 tumor suppressor, by using RNAseq technology.
2014-07-29 | GSE59855 | GEO
Project description:Chemotherapy resistance is a relevant clinical issue in the tumor treatment, in particular in biliary tract carcinoma (BTC), for which there are no effective therapies, neither in the first nor in the second line. The development of chemoresistant cell lines as experimental models to investigate the mechanisms of resistance and identify alternative druggable pathways is mandatory. In BTC, in which genetics and biological behavior depend on the etiology, ethnicity and anatomical site of origin, the creation of models that better recapitulate these characteristics is even more crucial. Here we have established and characterized an intrahepatic cholangiocarcinoma (iCCA) cell line derived from an Italian patient, called 82.3. Cells were isolated from a patient-derived xenograft and, after establishment, immunophenotypic, biological, genetic, molecular characteristics and tumorigenicity in vivo in NOD/SCID mice were investigated. 82.3 cells exhibited epithelial morphology and cell markers (EPCAM, CK7 and 19); they also expressed different cancer stem markers (CD44, CD133, CD49b, CD24, Stro1, PAX6, FOXA2, OCT3 / 4) and under anchorage-independent and serum-free conditions were capable of originating cholangiospheres. The population doubling time was approximately 53 hours. In vitro they demonstrated a poor ability to migrate, but in vivo, 82.3 cells retained their tumorigenicity, with a long latency period (16 weeks). Genetic identity using DNA fingerprinting analysis revealed 16 different loci and the cell line was characterized by a complex hyperdiploid karyotype. Furthermore, 82.3 cells showed cross-resistance to gemcitabine, 5-fluorouracil, carboplatin and oxaliplatin; in fact their genetic profile showed that in a panel of genes (n = 168), specific for drug resistance and related to the epithelial-mesenchymal transition, 60% of them were deregulated in 82.3 cells compared to a control iCCA cell line sensitive to chemotherapeutics. In conclusion, we have created new iCCA cell line of Caucasian origin that could be exploited as a preclinical model to study drug resistance mechanisms and to identify alternative therapies to improve the prognosis of this tumor type.
2021-05-01 | GSE171148 | GEO