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


METHODS
Tumor 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.


RESULTS
Among 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.


CONCLUSIONS
The 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.
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China ; Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China.
Phyllis F Y
PF
Cheung
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China ; Department of Surgery, The University of Hong Kong, Hong Kong, China ; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.
Chi Wai
CW
Yip
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Linda W C
LW
Ng
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China.
Kwok Wai
KW
Lo
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China.
Chit
C
Chow
Department of Pathology, Tuen Mun Hospital, Hong Kong, China.
Kui Fat
KF
Chan
Department of Surgery, The University of Hong Kong, Hong Kong, China.
Tan To
TT
Cheung
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China ; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Siu Tim
0000-0003-2147-315X
ST
Cheung
Cell line establishment; Hepatocellular carcinoma; Patient-derived xenograft