Molecular Biologic Characteristics and Relationship with Hepatocellular Carcinoma of Oval Cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHANGPeng , ZHUXiao-feng ,  JIAOXing-yuan

Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China;

Corresponding author：

JIAOXing-yuan, Email: jiaoxingyuan@hotmail.com

Keywords：

Hepatocellular carcinoma; Hepatic oval cells; Stem cell; Marker; Prognosis

DOI：

10.7507/1007-9424.20150130

Video：

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Objective To introduce the general situation about oval cells and the advance in research on relation between the hepatic oval cells and hepatocellular carcinoma (HCC). Method Relevant literatures in recent years about oval cells in hepatocellular carcinoma were collected and analyzed. Results Hepatic oval cells are progenies of the hepatic stem cells that are thought to reside in the terminal branches of the biliary tree, termed the canals of Hering.After severe liver injury resulting in hepatocyte and cholangiocyte necrosis/apoptosis, the dual-potential oval cells will proliferate and differentiate into hepatocytes or cholangiocytes to replace the respective lost cell types.Recent studies have found many new oval cell surface markers, and promoted the recognition of oval cells.The level of oval cells proliferation is positively correlated with the malignant and inflammatory level of chronic liver diseases.More importantly, oval cells is involved in the occurrence, development, recurrence, and metastasis of liver cancer, and closely related to the prognosis of HCC. Conclusion An improved understanding of the biological behavior of hepatic oval cells may lead to the development of novel diagnosis, treatment regimens, and prevention for hepatocellular carcinoma.

Citation： ZHANGPeng, ZHUXiao-feng, JIAOXing-yuan. Molecular Biologic Characteristics and Relationship with Hepatocellular Carcinoma of Oval Cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(4): 494-498. doi: 10.7507/1007-9424.20150130 Copy

1.	Opie EL.The pathogenesis of tumors of the liver produced by butter yellow.J Exp Med, 1944, 80(3):231-246.
2.	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(2):142-148.
3.	胡荣林, 焦兴元, 黄庆.肝卵圆细胞分化过程中SDF-1/CXCR4轴的作用研究进展.中华外科杂志, 2011, 49(6):558-560.
4.	Radaeva (Pronina) SA, Faktor VM.The differentiation of oval cells into hepatocytes during induced hepatic carcinogenesis in mice.An electron microscopic study.Tsitologiia, 1990, 32(4):331-336.
5.	Faktor VM, Radaeva SA.The formation of oval-cell ducts during hepatic carcinogenesis in mice.Its relationship to the pre-existing canals of Hering.Ontogenez, 1992, 23(4):407-418.
6.	Burke ZD, Shen CN, Ralphs KL, et al.Characterization of liver function in transdifferentiated hepatocytes.J Cell Physiol, 2006, 206(1):147-159.
7.	Oh SH, Witek RP, Bae SH, et al.Bone marrow-derived hepatic oval cells differentiate into hepatocytes in 2-acetylaminofluorene/partial hepatectomy-induced liver regeneration.Gastroenterology, 2007, 132(3):1077-1087.
8.	Kubota K, Soeda J, Misawa R, et al.Bone marrow-derived cells fuse with hepatic oval cells but are not involved in hepatic tumorigenesis in the choline-deficient ethionine-supplemented diet rat model.Carcinogenesis, 2008, 29(2):448-454.
9.	Runge D, Runge DM, Jager D, et al.Serum-free, longterm cultures of human hepatocytes:maintenance of cell morphology, transcription factors, and liver-specific functions.Biochem Biophys Res Commun, 2000, 269(1):46-53.
10.	Szabó E, Lódi C, Korpos E, et al.Expression of matrilin-2 in oval cells during rat liver regeneration.Matrix Biol, 2007, 26(7):554-560.
11.	Yovchev MI, Grozdanov PN, Joseph B, et al.Novel hepatic progenitor cell surface markers in the adult rat liver.Hepatology, 2007, 45(1):139-149.
12.	Grozdanov PN, Yovchev MI, Dabeva MD.The oncofetal protein glypican-3 is a novel marker of hepatic progenitor/oval cells.Lab Invest, 2006, 86(12):1272-1284.
13.	Shiota G, Kunisada T, Oyama K, et al.In vivo transfer of hepatocyte growth factor gene accelerates proliferation of hepatic oval cells in a 2-acetylaminofluorene/partial hepatectomy model in rats.FEBS Lett, 2000, 470(3):325-330.
14.	黄晓明, 焦兴元, 曾三平, 等.SDF-1/CXCR4在大鼠肝卵圆细胞增殖过程中的表达及意义.中国普外基础与临床杂志, 2008, 15(7):489-493, 497.
15.	Ise N, Sato T, Yasui O, et al.Enhanced proliferation of hepatic progenitor cells in rats after portal branch occlusion.Liver Transpl, 2004, 0(6):748-754.
16.	Tanaka M, Miyajima A.Identification and isolation of adult liver stem/progenitor cells.Methods Mol Biol, 2012, 826:25-32.
17.	Qin AL, Zhou XQ, Zhang W, et al.Characterization and enrichment of hepatic progenitor cells in adult rat liver.World J Gastroenterol, 2004, 10(10):1480-1486.
18.	Erker L, Grompe M.Signaling networks in hepatic oval cell activation.Stem Cell Res, 2007, 1(2):90-102.
19.	Oben JA, Roskams T, Yang S, et al.Hepatic fibrogenesis requires sympathetic neurotransmitters.Gut, 2004, 53(3):438-445.
20.	黄晓明, 焦兴元, 曾三平, 等.肝卵圆细胞分化过程中SDF-1/CXCR4生物轴的作用研究.中华普通外科学文献:电子版, 2008, 2(3):190-196.
21.	黄庆, 焦兴元, 胡以则.肝卵圆细胞激活和增殖过程中Wnt/β-catenin通路的研究进展.中华肝胆外科杂志, 2012, 18(3):235-238.
22.	Lee KP, Lee JH, Kim TS, et al.The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis.Proc Natl Acad Sci USA, 2010, 107(18):8248-8253.
23.	Darwiche H, Oh SH, Steiger-Luther NC, et al.Inhibition of Notch signaling affects hepatic oval cell response in rat model of 2AAF-PH.Hepat Med, 2011, 3:89-98.
24.	Chen L, Zhang W, Liang HF, et al.Activin A induces growth arrest through a SMAD-dependent pathway in hepatic progenitor cells.Cell Commun Signal, 2014, 12:18.
25.	Chen XG, Xu CS, Liu YM.Involvement of ERK1/2 signaling in proliferation of eight liver cell types during hepatic regeneration in rats.Genet Mol Res, 2013, 12(1):665-677.
26.	Okano J, Shiota G, Matsumoto K, et al.Hepatocyte growth factor exerts a proliferative effect on oval cells through the PI3K/AKT signaling pathway.Biochem Biophys Res Commun, 2003, 309(2):298-304.
27.	Parkin DM, Bray F, Ferlay J, et al.Estimating the world cancer burden:Globocan 2000.Int J Cancer, 2001, 94(2):153-156.
28.	Sell S.Cellular origin of cancer:dedifferentiation or stem cell maturation arrest? Environ Health Perspect, 1993, 101 Suppl 5:15-26.
29.	Sell S, Leffert HL.Liver cancer stem cells.J Clin Oncol, 2008, 26(17):2800-2805.
30.	Yoshimura H, Harris R, Yokoyama S, et al.Anaplastic carcinomas in nude mice and in original donor strain rats inoculated with cultured oval cells.Am J Pathol, 1983, 110(3):322-332.
31.	Richards WG, Yoder BK, Isfort RJ, et al.Oval cell proliferation associated with the murine insertional mutation TgN737Rpw.Am J Pathol, 1996, 149(6):1919-1930.
32.	陈琼荣, 向锦, 廖冰, 等.卵圆细胞在实验性肝癌发生过程中的演变特征.癌症, 2007, 26(7):719-723.
33.	de Lima VM, Oliveira CP, Alves VA, et al.A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma.J Hepatol, 2008, 49(6):1055-1061.
34.	Fan L, Xu C, Wang C, et al.Bmi1 is required for hepatic progenitor cell expansion and liver tumor development.PLoS One, 2012, 7(9):e46472.
35.	Li CH, Wang YJ, Dong W, et al.Hepatic oval cell lines generate hepatocellular carcinoma following transfection with HBx gene and treatment with aflatoxin B1 in vivo.Cancer Lett, 2011, 311(1):1-10.
36.	Li X, Li Y, Kang X, et al.Dynamic alteration of protein expression profiles during neoplastic transformation of rat hepatic oval-like cells.Cancer Sci, 2010, 101(5):1099-1107.
37.	Yang XR, Xu Y, Yu B, et al.High expression levels of putative hepatic stem/progenitor cell biomarkers related to tumour angiogenesis and poor prognosis of hepatocellular carcinoma.Gut, 2010, 59(7):953-962.
38.	Yeh CT, Kuo CJ, Lai MW, et al.CD133-positive hepatocellular carcinoma in an area endemic for hepatitis B virus infection.BMC Cancer, 2009, 9:324.
39.	Kim H, Choi GH, Na DC, et al.Human hepatocellular carcinomas with "Stemness"-related marker expression:keratin 19 expression and a poor prognosis.Hepatology, 2011, 54(5):1707-1717.
40.	Kim H, Yoo JE, Cho JY, et al.Telomere length, TERT and shelterin complex proteins in hepatocellular carcinomas expressing "stemness"-related markers.J Hepatol, 2013, 59(4):746-752.
41.	Wu PC, Fang JW, Lau VK, et al.Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers.Clinical and biological implications.Am J Pathol, 1996, 149(4):1167-1175.
42.	Durnez A, Verslype C, Nevens F, et al.The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma.A possible progenitor cell origin.Histopathology, 2006, 49(2):138-151.
43.	Woo HG, Lee JH, Yoon JH, et al.Identification of a cholangiocar-cinoma-like gene expression trait in hepatocellular carcinoma.Cancer Res, 2010, 70(8):3034-3041.
44.	Oliva J, French BA, Qing X, et al.The identification of stem cells in human liver diseases and hepatocellular carcinoma.Exp Mol Pathol, 2010, 88(3):331-340.
45.	Ziol M, Nault JC, Aout M, et al.Intermediate hepatobiliary cells predict an increased risk of hepatocarcinogenesis in patients with hepatitis C virus-related cirrhosis.Gastroenterology, 2010, 139(1):335-343.e2.
46.	Lowes KN, Brennan BA, Yeoh GC, et al.Oval cell numbers in human chronic liver diseases are directly related to disease severity.Am J Pathol, 1999, 154(2):537-541.
47.	Tsamandas AC, Syrokosta I, Thomopoulos K, et al.Potential role of hepatic progenitor cells expression in cases of chronic hepatitis C and their relation to response to therapy:a clinicopathologic study.Liver Int, 2006, 26(7):817-826.

1. Opie EL.The pathogenesis of tumors of the liver produced by butter yellow.J Exp Med, 1944, 80(3):231-246.
2. 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(2):142-148.
3. 胡荣林, 焦兴元, 黄庆.肝卵圆细胞分化过程中SDF-1/CXCR4轴的作用研究进展.中华外科杂志, 2011, 49(6):558-560.
4. Radaeva (Pronina) SA, Faktor VM.The differentiation of oval cells into hepatocytes during induced hepatic carcinogenesis in mice.An electron microscopic study.Tsitologiia, 1990, 32(4):331-336.
5. Faktor VM, Radaeva SA.The formation of oval-cell ducts during hepatic carcinogenesis in mice.Its relationship to the pre-existing canals of Hering.Ontogenez, 1992, 23(4):407-418.
6. Burke ZD, Shen CN, Ralphs KL, et al.Characterization of liver function in transdifferentiated hepatocytes.J Cell Physiol, 2006, 206(1):147-159.
7. Oh SH, Witek RP, Bae SH, et al.Bone marrow-derived hepatic oval cells differentiate into hepatocytes in 2-acetylaminofluorene/partial hepatectomy-induced liver regeneration.Gastroenterology, 2007, 132(3):1077-1087.
8. Kubota K, Soeda J, Misawa R, et al.Bone marrow-derived cells fuse with hepatic oval cells but are not involved in hepatic tumorigenesis in the choline-deficient ethionine-supplemented diet rat model.Carcinogenesis, 2008, 29(2):448-454.
9. Runge D, Runge DM, Jager D, et al.Serum-free, longterm cultures of human hepatocytes:maintenance of cell morphology, transcription factors, and liver-specific functions.Biochem Biophys Res Commun, 2000, 269(1):46-53.
10. Szabó E, Lódi C, Korpos E, et al.Expression of matrilin-2 in oval cells during rat liver regeneration.Matrix Biol, 2007, 26(7):554-560.
11. Yovchev MI, Grozdanov PN, Joseph B, et al.Novel hepatic progenitor cell surface markers in the adult rat liver.Hepatology, 2007, 45(1):139-149.
12. Grozdanov PN, Yovchev MI, Dabeva MD.The oncofetal protein glypican-3 is a novel marker of hepatic progenitor/oval cells.Lab Invest, 2006, 86(12):1272-1284.
13. Shiota G, Kunisada T, Oyama K, et al.In vivo transfer of hepatocyte growth factor gene accelerates proliferation of hepatic oval cells in a 2-acetylaminofluorene/partial hepatectomy model in rats.FEBS Lett, 2000, 470(3):325-330.
14. 黄晓明, 焦兴元, 曾三平, 等.SDF-1/CXCR4在大鼠肝卵圆细胞增殖过程中的表达及意义.中国普外基础与临床杂志, 2008, 15(7):489-493, 497.
15. Ise N, Sato T, Yasui O, et al.Enhanced proliferation of hepatic progenitor cells in rats after portal branch occlusion.Liver Transpl, 2004, 0(6):748-754.
16. Tanaka M, Miyajima A.Identification and isolation of adult liver stem/progenitor cells.Methods Mol Biol, 2012, 826:25-32.
17. Qin AL, Zhou XQ, Zhang W, et al.Characterization and enrichment of hepatic progenitor cells in adult rat liver.World J Gastroenterol, 2004, 10(10):1480-1486.
18. Erker L, Grompe M.Signaling networks in hepatic oval cell activation.Stem Cell Res, 2007, 1(2):90-102.
19. Oben JA, Roskams T, Yang S, et al.Hepatic fibrogenesis requires sympathetic neurotransmitters.Gut, 2004, 53(3):438-445.
20. 黄晓明, 焦兴元, 曾三平, 等.肝卵圆细胞分化过程中SDF-1/CXCR4生物轴的作用研究.中华普通外科学文献:电子版, 2008, 2(3):190-196.
21. 黄庆, 焦兴元, 胡以则.肝卵圆细胞激活和增殖过程中Wnt/β-catenin通路的研究进展.中华肝胆外科杂志, 2012, 18(3):235-238.
22. Lee KP, Lee JH, Kim TS, et al.The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis.Proc Natl Acad Sci USA, 2010, 107(18):8248-8253.
23. Darwiche H, Oh SH, Steiger-Luther NC, et al.Inhibition of Notch signaling affects hepatic oval cell response in rat model of 2AAF-PH.Hepat Med, 2011, 3:89-98.
24. Chen L, Zhang W, Liang HF, et al.Activin A induces growth arrest through a SMAD-dependent pathway in hepatic progenitor cells.Cell Commun Signal, 2014, 12:18.
25. Chen XG, Xu CS, Liu YM.Involvement of ERK1/2 signaling in proliferation of eight liver cell types during hepatic regeneration in rats.Genet Mol Res, 2013, 12(1):665-677.
26. Okano J, Shiota G, Matsumoto K, et al.Hepatocyte growth factor exerts a proliferative effect on oval cells through the PI3K/AKT signaling pathway.Biochem Biophys Res Commun, 2003, 309(2):298-304.
27. Parkin DM, Bray F, Ferlay J, et al.Estimating the world cancer burden:Globocan 2000.Int J Cancer, 2001, 94(2):153-156.
28. Sell S.Cellular origin of cancer:dedifferentiation or stem cell maturation arrest? Environ Health Perspect, 1993, 101 Suppl 5:15-26.
29. Sell S, Leffert HL.Liver cancer stem cells.J Clin Oncol, 2008, 26(17):2800-2805.
30. Yoshimura H, Harris R, Yokoyama S, et al.Anaplastic carcinomas in nude mice and in original donor strain rats inoculated with cultured oval cells.Am J Pathol, 1983, 110(3):322-332.
31. Richards WG, Yoder BK, Isfort RJ, et al.Oval cell proliferation associated with the murine insertional mutation TgN737Rpw.Am J Pathol, 1996, 149(6):1919-1930.
32. 陈琼荣, 向锦, 廖冰, 等.卵圆细胞在实验性肝癌发生过程中的演变特征.癌症, 2007, 26(7):719-723.
33. de Lima VM, Oliveira CP, Alves VA, et al.A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma.J Hepatol, 2008, 49(6):1055-1061.
34. Fan L, Xu C, Wang C, et al.Bmi1 is required for hepatic progenitor cell expansion and liver tumor development.PLoS One, 2012, 7(9):e46472.
35. Li CH, Wang YJ, Dong W, et al.Hepatic oval cell lines generate hepatocellular carcinoma following transfection with HBx gene and treatment with aflatoxin B1 in vivo.Cancer Lett, 2011, 311(1):1-10.
36. Li X, Li Y, Kang X, et al.Dynamic alteration of protein expression profiles during neoplastic transformation of rat hepatic oval-like cells.Cancer Sci, 2010, 101(5):1099-1107.
37. Yang XR, Xu Y, Yu B, et al.High expression levels of putative hepatic stem/progenitor cell biomarkers related to tumour angiogenesis and poor prognosis of hepatocellular carcinoma.Gut, 2010, 59(7):953-962.
38. Yeh CT, Kuo CJ, Lai MW, et al.CD133-positive hepatocellular carcinoma in an area endemic for hepatitis B virus infection.BMC Cancer, 2009, 9:324.
39. Kim H, Choi GH, Na DC, et al.Human hepatocellular carcinomas with "Stemness"-related marker expression:keratin 19 expression and a poor prognosis.Hepatology, 2011, 54(5):1707-1717.
40. Kim H, Yoo JE, Cho JY, et al.Telomere length, TERT and shelterin complex proteins in hepatocellular carcinomas expressing "stemness"-related markers.J Hepatol, 2013, 59(4):746-752.
41. Wu PC, Fang JW, Lau VK, et al.Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers.Clinical and biological implications.Am J Pathol, 1996, 149(4):1167-1175.
42. Durnez A, Verslype C, Nevens F, et al.The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma.A possible progenitor cell origin.Histopathology, 2006, 49(2):138-151.
43. Woo HG, Lee JH, Yoon JH, et al.Identification of a cholangiocar-cinoma-like gene expression trait in hepatocellular carcinoma.Cancer Res, 2010, 70(8):3034-3041.
44. Oliva J, French BA, Qing X, et al.The identification of stem cells in human liver diseases and hepatocellular carcinoma.Exp Mol Pathol, 2010, 88(3):331-340.
45. Ziol M, Nault JC, Aout M, et al.Intermediate hepatobiliary cells predict an increased risk of hepatocarcinogenesis in patients with hepatitis C virus-related cirrhosis.Gastroenterology, 2010, 139(1):335-343.e2.
46. Lowes KN, Brennan BA, Yeoh GC, et al.Oval cell numbers in human chronic liver diseases are directly related to disease severity.Am J Pathol, 1999, 154(2):537-541.
47. Tsamandas AC, Syrokosta I, Thomopoulos K, et al.Potential role of hepatic progenitor cells expression in cases of chronic hepatitis C and their relation to response to therapy:a clinicopathologic study.Liver Int, 2006, 26(7):817-826.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Molecular Biologic Characteristics and Relationship with Hepatocellular Carcinoma of Oval Cells

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