GSE171148
A novel multidrug-resistant cell line from an Italian intrahepatic cholangiocarcinoma patient
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. Overall design: Transcriptomic analysis of two multidrug resistant cholangiocarcinoma cell lines, 82.3 and MT-CHC01R1.5, compared to the sensible MT-CHC01 cell line