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Journal of Cancer Research and Clinical Oncology

Published in:

01-11-2008 | Original Paper

Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials

Authors: Guo-Ming Shi, Yang Xu, Jia Fan, Jian Zhou, Xin-Rong Yang, Shuang-Jian Qiu, Yong Liao, Wei-Zhong Wu, Yuan Ji, Ai-Wu Ke, Zhen-Bin Ding, Yi-Zhou He, Bing Wu, Guo-Huan Yang, Wen-Zhen Qin, Wu Zhang, Jiang Zhu, Zhi-Hui Min, Zhi-Quan Wu

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2008

Abstract

Purpose

To identify the side population (SP) cells from four hepatocellular carcinoma (HCC) cell lines with stepwise metastatic potentials.

Methods

SP cells were sorted from HCCLM3, MHCC97-H, MHCC97-L and Hep3B by flow cytometry, and then analyzed by differentiation study, clonogenic assay, chemoresistance study and tumorigenicity assay in vivo. The expression of ABCG₂ in SP cells was detected by immunocytochemistry, western blotting and real-time quantitative PCR, respectively.

Results

There was significant difference in SP proportion among HCCLM3, MHCC97-H, MHCC97-L and Hep3B (28.7 ± 1.6%, 14.5 ± 0.6%, 4.2 ± 0.4%, 0.9 ± 0.1%, respectively, P < 0.01). All the SP cells showed similar characteristics of self-renewal, high clonogenicity, remarkable chemo-resistance and high expression of ABCG₂. As low as 2,000 SP cells could initiate tumors in non-obese diabetic/severe combined immunodeficiency mice successfully.

Conclusions

SP cells purified from HCC cell lines harbors cancer stem cell-like properties, and may be related to the metastatic potentials and therapeutic-resistance of HCC.

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988PubMedCrossRef

Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, Iwama A, Nakauchi H, Taniguchi H (2006) Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology 44:240–251PubMedCrossRef

Dan YY, Riehle KJ, Lazaro C, Teoh N, Haque J, Campbell JS, Fausto N (2006) Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages. Proc Natl Acad Sci USA 103:9912–9917PubMedCrossRef

de Paiva CS, Chen Z, Corrales RM, Pflugfelder SC, Li DQ (2005) ABCG2 transporter identifies a population of clonogenic human limbal epithelial cells. Stem Cells 23:63–73PubMedCrossRef

Dennis JE, Esterly K, Awadallah A, Parrish CR, Poynter GM, Goltry KL (2007) Clinical-scale expansion of a mixed population of bone-marrow-derived stem and progenitor cells for potential use in bone-tissue regeneration. Stem Cells 25:2575–2582PubMedCrossRef

Ghods AJ, Irvin D, Liu G, Yuan X, Abdulkadir IR, Tunici P, Konda B, Wachsmann-Hogiu S, Black KL, Yu JS (2007) Spheres isolated from 9L gliosarcoma rat cell line possess chemoresistant and aggressive cancer stem-like cells. Stem Cells 25:1645–1653PubMedCrossRef

Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183:1797–1806PubMedCrossRef

Haraguchi N, Utsunomiya T, Inoue H, Tanaka F, Mimori K, Barnard GF, Mori M (2006) Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 24:506–513PubMedCrossRef

Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, Goodell MA, Brenner MK (2004) A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101:14228–14233PubMedCrossRef

Ho MM, Ng AV, Lam S, Hung JY (2007) Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res 67:4827–4833PubMedCrossRef

Kondo T, Setoguchi T, Taga T (2004) Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA 101:781–786PubMedCrossRef

Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, Mikaelyan A, Roberts LR, Demetris AJ, Sun Z (2006) A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 12:410–416PubMedCrossRef

Li F, Tiede B, Massague J, Kang Y (2007) Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res 17:3–14PubMedCrossRef

Li Y, Tang ZY, Ye SL, Liu YK, Chen J, Xue Q, Chen J, Gao DM, Bao WH (2001) Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol 7:630–636PubMed

Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF (2007) The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med 356:217–226PubMedCrossRef

Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, Zheng BJ, Guan XY (2007) Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 132:2542–2556PubMedCrossRef

Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108PubMedCrossRef

Scharenberg CW, Harkey MA, Torok-Storb B (2002) The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood 99:507–512PubMedCrossRef

Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401PubMedCrossRef

Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H (2006) Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun 351:820–824PubMedCrossRef

Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, Dombkowski D, Preffer F, Maclaughlin DT, Donahoe PK (2006) Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci USA 103:11154–11159PubMedCrossRef

Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, Wang L, Zhou J, Qiu SJ, Li Y (2004) A decade’s studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol 130:187–196PubMedCrossRef

Wang J, Guo LP, Chen LZ, Zeng YX, Lu SH (2007) Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res 67:3716–3724PubMedCrossRef

Wu C, Wei Q, Utomo V, Nadesan P, Whetstone H, Kandel R, Wunder JS, Alman BA (2007a) Side population cells isolated from mesenchymal neoplasms have tumor initiating potential. Cancer Res 67:8216–8222PubMedCrossRef

Wu X, Fan J, Wang X, Zhou J, Qiu S, Yu Y, Liu Y, Tang Z (2007b) Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion. Biochem Biophys Res Commun 355:866–871PubMedCrossRef

Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, Chu PW, Lam CT, Poon RT, Fan ST (2008a) Significance of CD90(+) cancer stem cells in human liver cancer. Cancer Cell 13:153–166PubMedCrossRef

Yang ZF, Ngai P, Ho DW, Yu WC, Ng MN, Lau CK, Li ML, Tam KH, Lam CT, Poon RT, Fan ST (2008b) Identification of local and circulating cancer stem cells in human liver cancer. Hepatology 47:919–928PubMedCrossRef

Ye QH, Qin LX, Forgues M, He P, Kim JW, Peng AC, Simon R, Li Y, Robles AI, Chen Y (2003) Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nature Med 9:416–423PubMedCrossRef

Yin S, Li J, Hu C, Chen X, Yao M, Yan M, Jiang G, Ge C, Xie H, Wan D (2007) CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer 120:1444–1450PubMedCrossRef

Zen Y, Fujii T, Yoshikawa S, Takamura H, Tani T, Ohta T, Nakanuma Y (2007) Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma. Am J Pathol 170:1750–1762PubMedCrossRef

Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7:1028–1034PubMedCrossRef

Title: Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials
Authors: Guo-Ming Shi
Yang Xu
Jia Fan
Jian Zhou
Xin-Rong Yang
Shuang-Jian Qiu
Yong Liao
Wei-Zhong Wu
Yuan Ji
Ai-Wu Ke
Zhen-Bin Ding
Yi-Zhou He
Bing Wu
Guo-Huan Yang
Wen-Zhen Qin
Wu Zhang
Jiang Zhu
Zhi-Hui Min
Zhi-Quan Wu
Publication date: 01-11-2008
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 11/2008
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-008-0407-1

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Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

Purpose

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Results

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