title: 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xin
authors.affiliation: Shanghai ChemPartner Co., LTD, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Shanghai ChemPartner Co., LTD, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.affiliation: Shanghai ChemPartner Co., LTD, Shanghai, China.
authors.forename: Fubo
authors.initials: F
authors.lastname: Xie
authors.affiliation: Shanghai ChemPartner Co., LTD, Shanghai, China.
authors.forename: Kedong
authors.initials: K
authors.lastname: Ouyang
authors.affiliation: Shanghai ChemPartner Co., LTD, Shanghai, China.
authors.forename: Xuzhen
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Minjun
authors.initials: M
authors.lastname: Wang
authors.affiliation: Shanghai ChemPartner Co., LTD, Shanghai, China.
authors.forename: Danyi
authors.initials: D
authors.lastname: Wen
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Yizhun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Shanghai ChemPartner Co., LTD, Shanghai, China.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Qin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002869:Chromosome Aberrations; D005260:Female; D018703:Founder Effect; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D007621:Karyotyping; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D061251:Primary Cell Culture; D020080:Tandem Repeat Sequences; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins