title: The properties of tumor-initiating cells from a hepatocellular carcinoma patient's primary and recurrent tumor.
abstract: Hepatocellular carcinoma (HCC) is associated with a high morbidity and mortality due to its high rate of recurrence. However, little is known about the biological characteristics of recurrent HCC cells. A single patient's primary and recurrent HCC-derived cell lines, Hep-11 and Hep-12, respectively, were established by primary culture. These two cell lines have the same hepatitis B virus integration site and share many common amplifications and deletions, which suggest that they have the same clonal origin. While Hep-11 cells were non-tumorigenic at 16 weeks following injection of up to 10 000 cells, injection of only 100 Hep-12 cells was sufficient to initiate tumor growth, and all single Hep-12 clones were tumorigenic in immunodeficient mice. Compared with Hep-11, Hep-12 cells expressed the oval cell markers AFP, NCAM/CD56, c-kit/CD117, as well as multiple stem cell markers such as Nanog, OCT4 and SOX2. In addition, >90% of Hep-12 cells were aldehyde dehydrogenase positive. They were also less resistant to paclitaxel, but more resistant to doxorubicin, cisplatin and hydroxycamptothecin (HCPT), which had been administrated to the patient. Furthermore, Hep-12 cells expressed higher levels of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1) than Hep-11, and PARP-1 inhibition potentiated the sensitivity to HCPT in Hep-12 cells but not in Hep-11 cells. These results indicate that a large population of the recurrent HCC-derived Hep-12 cells were tumor-initiating cells and that elevated expression of PARP-1 was related to their resistance to HCPT.
authors.affiliation: National Key Laboratory of Protein Engineering and Plant Gene Engineering, Institute of Life Science, Peking University, Beijing, China.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Xu
authors.forename: Bao-Cai
authors.initials: BC
authors.lastname: Xing
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Han
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Mei-Hao
authors.initials: MH
authors.lastname: Hu
authors.forename: Zuo-Liang
authors.initials: ZL
authors.lastname: Xu
authors.forename: Ji-You
authors.initials: JY
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Xie
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhi-Qian
authors.initials: ZQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002166:Camptothecin / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002945:Cisplatin / Q000008:administration & dosage; D055028:Comparative Genomic Hybridization; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000008:administration & dosage; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D004317:Doxorubicin; D011065:Poly(ADP-ribose) Polymerases; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin