Comprehensive characterization of the patient-derived xenograft and the paralleled primary hepatocellular carcinoma cell line.

Phyllis F Y Cheung,Chi Wai Yip,Kui Fat Chan,Tan To Cheung,Kwok Wai Lo,Chit Chow,Siu Tim Cheung,Linda W C Ng

doi:10.1186/s12935-016-0322-5

Abstract

BackgroundHepatocellular carcinoma (HCC) is an aggressive cancer with high mortality and morbidity worldwide. The limited clinically relevant model has impeded the development of effective HCC treatment strategy. Patient-derived xenograft (PDX) models retain most of the characteristics of original tumors and were shown to be highly predictive for clinical outcomes. Notably, primary cell line models allow in-depth molecular characterization and high-throughput analysis. Combined usage of the two models would provide an excellent tool for systematic study of therapeutic strategies. Here, we comprehensively characterized the novel PDX and the paralleled primary HCC cell line model.MethodsTumor tissues were collected from HCC surgical specimens. HCC cells were sorted for in vivo PDX and in vitro cell line establishment by the expression of hepatic cancer stem cell marker to enhance cell viability and the rate of success on subsequent culture. The PDX and its matching primary cell line were authenticated and characterized in vitro and in vivo.ResultsAmong the successful cases for generating PDXs and primary cells, HCC40 is capable for both PDX and primary cell line establishment, which were then further characterized. The novel HCC40-PDX and HCC40-CL exhibited consistent phenotypic characteristics as the original tumor in terms of HBV protein and AFP expressions. In common with HCC40-PDX, HCC40-CL was tumorigenic in immunocompromised mice. The migration ability in vitro and metastatic properties in vivo echoed the clinical feature of venous infiltration. Genetic profiling by short tandem repeat analysis and p53 mutation pattern consolidated that both the HCC40-PDX and HCC40-CL models were derived from the HCC40 clinical specimen.ConclusionsThe paralleled establishment of PDX and primary cell line would serve as useful models in comprehensive studies for HCC pathogenesis and therapeutics development for personalized treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-016-0322-5) contains supplementary material, which is available to authorized users.

Highlights

Hepatocellular carcinoma (HCC) is an aggressive cancer with high mortality and morbidity worldwide
Patientderived xenograft (PDX) and primary cell line establishment from fresh HCC tumor tissues Fresh tumor tissues from 24 HCC patients were included for PDX and cell line establishment
The in vitro spheroid formation and differentiation ability, and the in vivo tumorigenicity of granulin-epithelin precursor (GEP)-expressing cells were described [26], and the workflow of PDX and cell line establishment was illustrated in Additional file 1: Figure S1

Summary

Introduction

Hepatocellular carcinoma (HCC) is an aggressive cancer with high mortality and morbidity worldwide. The limited clinically relevant model has impeded the development of effective HCC treatment strategy. Patientderived xenograft (PDX) models retain most of the characteristics of original tumors and were shown to be highly predictive for clinical outcomes. Primary cell line models allow in-depth molecular characterization and high-throughput analysis. We comprehensively characterized the novel PDX and the paralleled primary HCC cell line model. Hepatocellular carcinoma (HCC) is an aggressive solid tumor with high mortality and morbidity rate worldwide [1]. The lack of clinically relevant models has impeded the development of effective HCC treatment strategy [3]. The major limitation of conventional cell line models is their poor predictive power on clinical outcome [3].

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Conclusion