nach oben

Hepatology International

Erschienen in:

02.05.2016 | Review Article

The potential role of liver stem cells in initiation of primary liver cancer

verfasst von: Xiao-Song Zhi, Jun Xiong, Xiao-Yuan Zi, Yi-Ping Hu

Erschienen in: Hepatology International | Ausgabe 6/2016

Einloggen, um Zugang zu erhalten

Abstract

Identification of the cellular origin of primary liver cancer remains challenging. Some data point toward liver stem cells (LSCs) or liver progenitor cells (LPCs) not only as propagators of liver regeneration, but also as initiators of liver cancer. LSCs exhibit a long lifespan and strong duplicative potential upon activation and are inclined to accumulate more mutations that can be passed down to the next generations. Recent evidence shows that dysregulation of signaling pathways associated with self-renewal of LSCs can drive their aberrant proliferation and even malignant transformation. If LSCs could be proved to be an initiator of liver carcinogenesis, they would be promising for ultra-early diagnosis and targeting therapy of liver cancer. This review mainly summarizes the potential role of LSCs in the carcinogenesis of primary liver cancer.

Smith A. A glossary for stem-cell biology. Nature 2006;441:1060

Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105–111

Whittaker S, Marais R, Zhu AX. The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 2010;29:4989–5005

Chiba T, Miyagi S, Saraya A, Aoki R, Seki A, Morita Y, Yonemitsu Y, et al. The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma. Cancer Res 2008;68:7742–7749

Fausto N. Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells. Hepatology 2004;39:1477–1487

Farber E. Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylamino-fluorene, and 3′-methyl-4-dimethylaminoazobenzene. Cancer Res 1956;16:142–148

Wilson JW, Leduc EH. Role of cholangioles in restoration of the liver of the mouse after dietary injury. J Pathol Bacteriol 1958;76:441–449

Shiojiri N, Lemire JM, Fausto N. Cell lineages and oval cell progenitors in rat liver development. Cancer Res 1991;51:2611–2620

Dabeva MD, Petkov PM, Sandhu J, Oren R, Laconi E, Hurston E, et al. Proliferation and differentiation of fetal liver epithelial progenitor cells after transplantation into adult rat liver. Am J Pathol 2000;156:2017–2031

10.

Fujio K, Evarts RP, Hu Z, Marsden ER, Thorgeirsson SS. Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat. Lab Invest 1994;70:511–516

11.

Fiegel HC, Park JJ, Lioznov MV, Martin A, Jaeschke-Melli S, Kaufmann PM, et al. Characterization of cell types during rat liver development. Hepatology 2003;37:148–154

12.

Golding M, Sarraf CE, Lalani EN, Anilkumar TV, Edwards RJ, Nagy P, et al. Oval cell differentiation into hepatocytes in the acetylaminofluorene-treated regenerating rat liver. Hepatology 1995;22:1243–1253

13.

Li WL, Su J, Yao YC, Tao XR, Yan YB, Yu HY, et al. Isolation and characterization of bipotent liver progenitor cells from adult mouse. Stem Cells 2006;24:322–332

14.

Lowes KN, Brennan BA, Yeoh GC, Olynyk JK. Oval cell numbers in human chronic liver diseases are directly related to disease severity. Am J Pathol 1999;154:537–541

15.

Lee TK, Castilho A, Ma S, Ng IO. Liver cancer stem cells: implications for a new therapeutic target. Liver Int 2009;29:955–965

16.

Taniguchi H, Kondo R, Suzuki A, Zheng YW, Takada Y, Fukunaga K, et al. Clonogenic colony-forming ability of flow cytometrically isolated hepatic progenitor cells in the murine fetal liver. Cell Transplant 2000;9:697–700

17.

Suzuki A, Sekiya S, Onishi M, Oshima N, Kiyonari H, Nakauchi H, et al. Flow cytometric isolation and clonal identification of self-renewing bipotent hepatic progenitor cells in adult mouse liver. Hepatology 2008;48:1964–1978

18.

Qiu Q, Hernandez JC, Dean AM, Rao PH, Darlington GJ. CD24-positive cells from normal adult mouse liver are hepatocyte progenitor cells. Stem Cells Dev 2011;20:2177–2188

19.

Kamiya A, Kakinuma S, Yamazaki Y, Nakauchi H. Enrichment and clonal culture of progenitor cells during mouse postnatal liver development in mice. Gastroenterology 2009; 137: 1114–1126, 1126.e1–1126.e14

20.

Okabe M, Tsukahara Y, Tanaka M, Suzuki K, Saito S, Kamiya Y, et al. Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver. Development 2009;136:1951–1960

21.

Tanaka M, Miyajima A. Identification and isolation of adult liver stem/progenitor cells. Methods Mol Biol 2012;826:25–32

22.

Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001;105:369–377

23.

Miyajima A, Tanaka M, Itoh T. Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming. Cell Stem Cell 2014;14:561–574

24.

Rodrigo-Torres D, Affo S, Coll M, Morales-Ibanez O, Millan C, Blaya D, et al. The biliary epithelium gives rise to liver progenitor cells. Hepatology 2014;60:1367–1377

25.

Tarlow BD, Finegold MJ, Grompe M. Clonal tracing of Sox9+ liver progenitors in mouse oval cell injury. Hepatology 2014;60:278–289

26.

Tarlow BD, Pelz C, Naugler WE, Wakefield L, Wilson EM, Finegold MJ, et al. Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes. Cell Stem Cell 2014;15:605–618

27.

Menthena A, Deb N, Oertel M, Grozdanov PN, Sandhu J, Shah S, et al. Bone marrow progenitors are not the source of expanding oval cells in injured liver. Stem Cells 2004;22:1049–1061

28.

Sell S. Cellular origin of cancer: dedifferentiation or stem cell maturation arrest? Environ Health Perspect 1993;101(Suppl 5):15–26

29.

Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 2014;506:328–333

30.

Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, et al. Identification of cells initiating human melanomas. Nature 2008;451:345–349

31.

O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007;445:106–110

32.

Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 2009;457:608–611

33.

Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 2012;337:730–735

34.

Roskams T. Liver stem cells and their implication in hepatocellular and cholangiocarcinoma. Oncogene 2006;25:3818–3822

35.

Sell S, Pierce GB. Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab Invest 1994;70:6–22

36.

Teebor GW, Becker FF. Regression and persistence of hyperplastic hepatic nodules induced by N-2-fluorenylacetamide and their relationship to hepatocarcinogenesis. Cancer Res 1971;31:1–3

37.

Alpini G, Aragona E, Dabeva M, Salvi R, Shafritz DA, Tavoloni N. Distribution of albumin and alpha-fetoprotein mRNAs in normal, hyperplastic, and preneoplastic rat liver. Am J Pathol 1992;141:623–632

38.

Sell S, Dunsford HA. Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma. Am J Pathol 1989;134:1347–1363

39.

Knight B, Akhurst B, Matthews VB, Ruddell RG, Ramm GA, Abraham LJ, et al. Attenuated liver progenitor (oval) cell and fibrogenic responses to the choline deficient, ethionine supplemented diet in the BALB/c inbred strain of mice. J Hepatol 2007;46:134–141

40.

Knight B, Lim R, Yeoh GC, Olynyk JK. Interferon-gamma exacerbates liver damage, the hepatic progenitor cell response and fibrosis in a mouse model of chronic liver injury. J Hepatol 2007;47:826–833

41.

Blanpain C. Tracing the cellular origin of cancer. Nat Cell Biol 2013;15:126–134

42.

Wang Y, Yang J, Zheng H, Tomasek GJ, Zhang P, McKeever PE, et al. Expression of mutant p53 proteins implicates a lineage relationship between neural stem cells and malignant astrocytic glioma in a murine model. Cancer Cell 2009;15:514–526

43.

Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell 2014;14:275–291

44.

Wang EY, Yeh SH, Tsai TF, Huang HP, Jeng YM, Lin WH, et al. Depletion of beta-catenin from mature hepatocytes of mice promotes expansion of hepatic progenitor cells and tumor development. Proc Natl Acad Sci USA 2011;108:18384–18389

45.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69–90

46.

Akiba J, Nakashima O, Hattori S, Tanikawa K, Takenaka M, Nakayama M, et al. Clinicopathologic analysis of combined hepatocellular-cholangiocarcinoma according to the latest WHO classification. Am J Surg Pathol 2013;37:496–505

47.

Coulouarn C, Cavard C, Rubbia-Brandt L, Audebourg A, Dumont F, Jacques S, et al. Combined hepatocellular-cholangiocarcinomas exhibit progenitor features and activation of Wnt and TGFbeta signaling pathways. Carcinogenesis 2012;33:1791–1796

48.

Yoshimura H, Harris R, Yokoyama S, Takahashi S, Sells MA, Pan SF, et al. Anaplastic carcinomas in nude mice and in original donor strain rats inoculated with cultured oval cells. Am J Pathol 1983;110:322–332

49.

Yeoh G, Porter I, Arcus M, Douglas A. Transformation of cultured fetal rat liver cells by MDAB and phenobarbital. Morphological, biochemical and immunocytochemical characterization of cell lines. Carcinogenesis 1989;10:1015–1027

50.

Libbrecht L, Roskams T. Hepatic progenitor cells in human liver diseases. Semin Cell Dev Biol 2002;13:389–396

51.

Lee ES, Han EM, Kim YS, Shin BK, Kim CH, Kim HK, et al. Occurrence of c-kit+ tumor cells in hepatitis B virus-associated hepatocellular carcinoma. Am J Clin Pathol 2005;124:31–36

52.

Guichard C, Imbeaud S, Amaddeo G, Ben Maad I, Letouze E, Pelletier L, et al. Landscape of somatic mutation in hepatocellular carcinoma. J Hepatol 2012;56:S8

53.

Kahn M. Can we safely target the WNT pathway? Nat Rev Drug Discov 2014;13:513–532

54.

Phesse TJ, Buchert M, Stuart E, Flanagan DJ, Faux M, Afshar-Sterle S, et al. Partial inhibition of gp130-Jak-Stat3 signaling prevents Wnt-beta-catenin-mediated intestinal tumor growth and regeneration. Sci Signal 2014;7:92

55.

Tang Q, Zou Z, Zou C, Zhang Q, Huang R, Guan X, et al. MicroRNA-93 suppress colorectal cancer development via Wnt/beta-catenin pathway downregulating. Tumour Biol 2015;36(3):1701–1710CrossRefPubMed

56.

Ma L, Ji L, Yu Y, Wang J. Novel molecular targets for diagnosis and treatment of hepatocellular carcinoma. Discov Med 2015;19:7–14

57.

Stancikova J, Krausova M, Kolar M, Fafilek B, Svec J, Sedlacek R, et al. NKD1 marks intestinal and liver tumors linked to aberrant Wnt signaling. Cell Signal 2015;27:245–256

58.

Wang C, Yang W, Yan HX, Luo T, Zhang J, Tang L, et al. Hepatitis B virus X (HBx) induces tumorigenicity of hepatic progenitor cells in 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated HBx transgenic mice. Hepatology 2012;55:108–120

59.

Shen L, Zhang X, Hu D, Feng T, Li H, Lu Y, et al. Hepatitis B virus X (HBx) play an anti-apoptosis role in hepatic progenitor cells by activating Wnt/beta-catenin pathway. Mol Cell Biochem 2013;383:213–222

60.

Yamashita T, Budhu A, Forgues M, Wang XW. Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma. Cancer Res 2007;67:10831–10839

61.

Yang W, Yan HX, Chen L, Liu Q, He YQ, Yu LX, et al. Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res 2008;68:4287–4295

62.

Mokkapati S, Niopek K, Huang L, Cunniff KJ, Ruteshouser EC, deCaestecker M, et al. beta-catenin activation in a novel liver progenitor cell type is sufficient to cause hepatocellular carcinoma and hepatoblastoma. Cancer Res 2014;74:4515–4525

63.

Harada N, Miyoshi H, Murai N, Oshima H, Tamai Y, Oshima M, et al. Lack of tumorigenesis in the mouse liver after adenovirus-mediated expression of a dominant stable mutant of beta-catenin. Cancer Res 2002;62:1971–1977

64.

Patel T. Cholangiocarcinoma—controversies and challenges. Nat Rev Gastroenterol Hepatol 2011;8:189–200

65.

Guest RV, Boulter L, Kendall TJ, Minnis-Lyons SE, Walker R, Wigmore SJ, et al. Cell lineage tracing reveals a biliary origin of intrahepatic cholangiocarcinoma. Cancer Res 2014;74:1005–1010

66.

Zender S, Nickeleit I, Wuestefeld T, Sorensen I, Dauch D, Bozko P, et al. A critical role for notch signaling in the formation of cholangiocellular carcinomas. Cancer Cell 2013;23:784–795

67.

Dill MT, Tornillo L, Fritzius T, Terracciano L, Semela D, Bettler B, et al. Constitutive Notch2 signaling induces hepatic tumors in mice. Hepatology 2013;57:1607–1619

68.

El Khatib M, Bozko P, Palagani V, Malek NP, Wilkens L, Plentz RR. Activation of Notch signaling is required for cholangiocarcinoma progression and is enhanced by inactivation of p53 in vivo. PLoS One 2013;8:e77433

69.

Villanueva A, Alsinet C, Yanger K, Hoshida Y, Zong Y, Toffanin S, et al. Notch signaling is activated in human hepatocellular carcinoma and induces tumor formation in mice. Gastroenterology 2012;143(1660–1669):e7

70.

Chan-On W, Nairismagi ML, Ong CK, Lim WK, Dima S, Pairojkul C, et al. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat Genet 2013;45:1474–1478

71.

Wang P, Dong Q, Zhang C, Kuan PF, Liu Y, Jeck WR, et al. Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas. Oncogene 2013;32:3091–3100

72.

Voss JS, Holtegaard LM, Kerr SE, Fritcher EG, Roberts LR, Gores GJ, et al. Molecular profiling of cholangiocarcinoma shows potential for targeted therapy treatment decisions. Hum Pathol 2013;44:1216–1222

73.

Saha SK, Parachoniak CA, Ghanta KS, Fitamant J, Ross KN, Najem MS, et al. Mutant IDH inhibits HNF-4alpha to block hepatocyte differentiation and promote biliary cancer. Nature 2014;513:110–114

74.

Saha SK, Parachoniak CA, Bardeesy N. IDH mutations in liver cell plasticity and biliary cancer. Cell Cycle 2014;13:3176–3182

75.

Yanger K, Zong Y, Maggs LR, Shapira SN, Maddipati R, Aiello NM, et al. Robust cellular reprogramming occurs spontaneously during liver regeneration. Genes Dev 2013;27:719–724

76.

Tanimizu N, Nishikawa Y, Ichinohe N, Akiyama H, Mitaka T. Sry HMG box protein 9-positive (Sox9+) epithelial cell adhesion molecule-negative (EpCAM-) biphenotypic cells derived from hepatocytes are involved in mouse liver regeneration. J Biol Chem 2014;289:7589–7598

77.

Sekiya S, Suzuki A. Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes. J Clin Invest 2012;122:3914–3918

78.

Gurlevik E, Fleischmann-Mundt B, Armbrecht N, Longerich T, Woller N, Kloos A, et al. Adjuvant gemcitabine therapy improves survival in a locally induced, R0-resectable model of metastatic intrahepatic cholangiocarcinoma. Hepatology 2013;58:1031–1041

79.

Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L. Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer 1985;55:124–135

80.

O’Connor K, Walsh JC, Schaeffer DF. Combined hepatocellular-cholangiocarcinoma (cHCC-CC): a distinct entity. Ann Hepatol 2014;13:317–322

81.

Dean FB, Hosono S, Fang L, Wu X, Faruqi AF, Bray-Ward P, et al. Comprehensive human genome amplification using multiple displacement amplification. Proc Natl Acad Sci USA 2002;99:5261–5266

82.

Maeda T, Adachi E, Kajiyama K, Sugimachi K, Tsuneyoshi M. Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features. Hum Pathol 1995;26:956–964

83.

Park HS, Bae JS, Jang KY, Lee JH, Yu HC, Jung JH, et al. Clinicopathologic study on combined hepatocellular carcinoma and cholangiocarcinoma: with emphasis on the intermediate cell morphology. J Korean Med Sci 2011;26:1023–1030

84.

Zhang F, Chen XP, Zhang W, Dong HH, Xiang S, Zhang WG, et al. Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence. Histopathology 2008;52:224–232

85.

Chiba T, Zheng YW, Kita K, Yokosuka O, Saisho H, Onodera M, et al. Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation. Gastroenterology 2007;133:937–950

86.

Ogasawara S, Akiba J, Nakayama M, Nakashima O, Torimura T, Yano H. Epithelial cell adhesion molecule-positive human hepatic neoplastic cells: development of combined hepatocellular-cholangiocarcinoma in mice. J Gastroenterol Hepatol 2015;30:413–420

87.

Changyong E, Xie Y, Yang Y, Ji D, Li W, Zhang X. Combined hepatocellular-cholangiocarcinoma with fever of unknown origin: a case report and review of literature. Cell Biochem Biophys 2014;69:1–6

88.

Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment. Ann Surg 1990;211:277–287

Titel: The potential role of liver stem cells in initiation of primary liver cancer
verfasst von: Xiao-Song Zhi
Jun Xiong
Xiao-Yuan Zi
Yi-Ping Hu
Publikationsdatum: 02.05.2016
Verlag: Springer India
Erschienen in: Hepatology International / Ausgabe 6/2016
Print ISSN: 1936-0533
Elektronische ISSN: 1936-0541
DOI: https://doi.org/10.1007/s12072-016-9730-9

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2016

Alcoholic hepatitis: should we combine old drugs for better results?

Elevated hepatic lipid and interferon stimulated gene expression in HCV GT3 patients relative to non-alcoholic steatohepatitis

Hepatitis C genotype 3 disease

Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China

A phase IIIb study of ledipasvir/sofosbuvir fixed-dose combination tablet in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 hepatitis C virus