Establishment and Characterization of 7 Novel Hepatocellular Carcinoma Cell Lines from Patient-Derived Tumor Xenografts

Abstract

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis worldwide and the molecular mechanism is not well understood. This study aimed to establish a collection of human HCC cell lines from patient-derived xenograft (PDX) models. From the 20 surgical HCC sample collections, 7 tumors were successfully developed in immunodeficient mice and further established 7 novel HCC cell lines (LIXC002, LIXC003, LIXC004, LIXC006, LIXC011, LIXC012 and CPL0903) by primary culture. The characterization of cell lines was defined by morphology, growth kinetics, cell cycle, chromosome analysis, short tandem repeat (STR) analysis, molecular profile, and tumorigenicity. Additionally, response to clinical chemotherapeutics was validated both in vitro and in vivo. STR analysis indicated that all cell lines were unique cells different from known cell lines and free of contamination by bacteria or mycoplasma. The other findings were quite heterogeneous between individual lines. Chromosome aberration could be found in all cell lines. Alpha-fetoprotein was overexpressed only in 3 out of 7 cell lines. 4 cell lines expressed high level of vimentin. Ki67 was strongly stained in all cell lines. mRNA level of retinoic acid induced protein 3 (RAI3) was decreased in all cell lines. The 7 novel cell lines showed variable sensitivity to 8 tested compounds. LIXC011 and CPL0903 possessed multiple drug resistance property. Sorafenib inhibited xenograft tumor growth of LIXC006, but not of LIXC012. Our results indicated that the 7 novel cell lines with low passage maintaining their clinical and pathological characters could be good tools for further exploring the molecular mechanism of HCC and anti-cancer drug screening.

First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway

“…31 ). According to our fi ndings that concurrent expression of FGF19 , FGFR4 , and KLB is necessary to convey sensitivity to BLU9931 in the HCC cell line panel ( Table 1 ), we fi rst confi rmed that the PDX-derived cell lines expressed FGF19 and FGFR4 at levels similar to those of the parental tumors ( Fig.…”

“…LIC0903, LIXC002, LIXC003, LIXC004, LIXC006, LIXC011, and LIXC012 (Shanghai ChemPartner Co., LTD; ref. 31 ) were grown in RPMI-1640 medium containing 10% FBS, 10 μg/mL insulin (Life Technologies), 2 μmol/L hydrocortisone, and 2.5 mg/mL glucose.…”

Review on near-infrared heptamethine cyanine dyes as theranostic agents for tumor imaging, targeting, and photodynamic therapy

“…49 On the other hand, the alternative in vitro screening of PDX-derived tumor cells often results in a loss of tumor cell subsets and information on tumor heterogeneity. 50 With the introduction of heptamethine cyanine dyes, we were able to characterize the PDX models by NIRF imaging by readily capturing subrenally grafted deep tissues. A wide spectrum of PDX models harboring different types of tumor samples, including gastric cancer, liver cancer, bladder cancer and renal cancer, were identified by NIRF imaging by the exclusive exhibition of fluorescence signals in the renal area of mice ( Fig.…”

Explant culture of sarcoma patients' tissue

“…35 Third, patient material could initially be expanded as PDX in mice that markedly increased the subsequent success in explant culture of colon cancer and hepatocellular carcinoma samples (Table 4). 34,39 In conclusion, the here described explant technique proved that patient-derived cell lines from different kinds of sarcoma entities can be established for use in preclinical studies and in personalized medicine.…”