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Liver Carcinogenesis pp 13–31Cite as

HGF and Liver Growth Regulation

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Part of the book series: NATO ASI Series ((ASIH,volume 88))

Abstract

Liver growth has fascinated scientists for many years, perhaps even centuries. Liver has a strong regenerative potential in response to toxic agents causing loss of hepatic parenchyma. Many chemical agents tested for carcinogenicity lead to formation of hepatic tumors. Other xenobiotic agents (e.g. anti-epileptics, hypolipidemic agents, barbiturates etc.) lead to a controlled expansion of hepatic mass above normal. Liver mass is gradually restored to normal upon discontinuation of the chemical, in a process accompanied by massive apoptosis. These and other phenomena have intensified interest in molecular mechanisms that control liver growth. The introduction of 2/3 partial hepatectomy as a systematic model for the study of liver regeneration in rats as shown by Higgins and Anderson (1931) led to a definition of phenomena related to liver regeneration which were well reproduced and became the guiding lines for research in the years that followed.

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References

  • Bisseil DM, Hammaker LE, Meyer UA. (1973) Parenchymal cells from adult rat liver in nonproliferating monolayer culture. I. Functional studies. J Cell Biol 59:722–734

    Article  Google Scholar 

  • Bucher NLR (1982) Thirty Years of Liver Regeneration: A distillate. In Cold Spring Harbor Conferences on Cell Proliferation, vol. 9 (Growth of cell in chemically defined media), p15–26

    Google Scholar 

  • Crookston KP, Webb DJ, Lamarre J, Gonias SL.(1993).Binding of platelet-derived growth factor-BB and transforming growth factor-beta 1 to alpha 2-macroglobulin in vitro and in vivo: comparison of receptor-recognized and non-recognized alpha 2-macroglobulin conformations. Biochem J 293:443–450.

    PubMed  CAS  Google Scholar 

  • de Hemptinne, B Lorge, Kestens PJ and Lambotte L (1985) Hepatocellular hyperpolarizing factors and regeneration after partial hepatectomy in the rat. Acta Gastroenterol Belg 48: 424–431

    PubMed  Google Scholar 

  • DuBois RD (1990) Early changes in gene expression during liver regeneration: what do they mean? Hepatology 6:1079–1082

    Article  Google Scholar 

  • Fisher B, Szuch P, Levine M, Fisher ER (1971) A portal blood factor as the humoral agent in liver regeneration. Science 171: 575–577

    Article  PubMed  CAS  Google Scholar 

  • Francavilla A, Starzl TE, Porter K, Foglieni CS, Michalopoulos GK, Carrieri G, Trejo Azzarone A, Barone M, Zeng QH (1991) Screening for candidate hepatic growth factors by selective portal infusion after canine Eck’s fistula. Hepatology 14:665–70.

    Article  PubMed  CAS  Google Scholar 

  • Grisham JW (1962) A morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating liver; autoradiography with thymidine-H3. Cancer Res 22: 842–849

    PubMed  CAS  Google Scholar 

  • Grisham JW, Leong GF, Hole BV (1964) Heterotopic partial autotransplantation of rat liver. Technique and demonstration of structure and function of the graft. Cancer Res 24: 1474–1482

    PubMed  CAS  Google Scholar 

  • Higgins GM, and Anderson RM (1931) Experimental pathology of the liver: I. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12: 186–202

    Google Scholar 

  • Jirtle RL, Michalopoulos G (1982) Effects of partial hepatectomy on transplanted hepatocytes. Cancer Res 42: 3000–3004

    PubMed  CAS  Google Scholar 

  • Keski-Oja J, Lohi J, Tuuttila A, Tryggvason K, Vartio T (1993) Proteolytic processing of the 72,000-Da type IV collagenase by urokinase plasminogen activator. Exp Cell Res 202:471–476

    Article  Google Scholar 

  • Kinoshita T, Hirao S, Matsumoto K, Nakamura T (1991) Possible endocrine control by hepatocyte growth factor of liver regeneration after partial hepatectomy. Biochem Biophys Res Commun 177:330–335.

    Article  PubMed  CAS  Google Scholar 

  • Kuwashima Y, Aoki K, Kohyyama K, Ishikawa T. (1990) Hepatocyte Regeneration after partial hepatectomy occurs even under several thrombocytopenic conditions in the rat. Jpn. J. Cancer Res 81:607–612.

    CAS  Google Scholar 

  • Lindroos P, Michalopoulos GK (1993) Response of phenobarbital- and ciprofibrate-exposed hepatocytes to growth factors in type I collagen gels. Carcinogenesis, 14:731–735

    Article  PubMed  CAS  Google Scholar 

  • Lindroos P, Tsai WH, Zarnegar R, Michalopoulos GK (1992) Plasma levels of HGF in rats treated with tumor promoters. Carcinogenesis 13:139–141

    Article  PubMed  CAS  Google Scholar 

  • Lindroos PM, Zarnegar R, Michalopoulos GK. (1991) Hepatic Growth Factor (Hepatopoietin A) Rapidly Increases in Plasma Prior to DNA Synthesis and Liver Regeneration Stimulated by Partial Hepatectomy and CCl4 Administration. Hepatology 13:743–750.

    Article  PubMed  CAS  Google Scholar 

  • Liu KX, Kato Y, Narukawa M, Kim DC, Hanano M, Higuchi O, Nakamura T, Sugiyama Y. (1992) Importance of the liver in plasma clearance of hepatocyte growth factors in rats. Am J Physiol 263:G642–9.

    PubMed  CAS  Google Scholar 

  • Liu M, Michalopoulos G (1994) Ehancement of DNA synthesis stimulated by HGF in normal livers after infusion of Collagenase. Hepatology, In Press.

    Google Scholar 

  • Liu Y, Michalopoulos GK, Zarnegar R. (1994) Structural and functional characterization of the mouse hepatocyte growth factor gene promoter. J Biol Chem 269:4152–4160

    PubMed  CAS  Google Scholar 

  • Lokker NA, Mark MR, Luis EA, Bennett GL, Robbins KA, Baker JB, Godowski PJ (1992) Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding. EMBO J 11:2503–2510.

    PubMed  CAS  Google Scholar 

  • Mars W, Zarnegar R, Michalopoulos G. (1993) Activation of Hepatocyte Growth Factor by the plasminogen activators uPA and tPA. Amer J Path 143:949–958.

    PubMed  CAS  Google Scholar 

  • Marsman DS, Goldsworthy TL, Popp JA (1992) Contrasting hepatocytic peroxisome proliferation, lipofuscin accumulation and cell turnover for the hepatocarcinogens Wy-14,643 and clofibric acid. Carcinogenesis 13:1011–1017

    Article  PubMed  CAS  Google Scholar 

  • Masumoto A, Yamamoto N (1991) Sequestration of a hepatocyte growth factor in extracellular matrix in normal adult rat liver. Biochem Biophys Res Commun 174:90–95

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto K, Nakamura T (1993) Roles of HGF as a pleiotropic factor in organ regeneration. Experientia Supplementa 65:225–249

    CAS  Google Scholar 

  • Matsumoto K, Okazaki H, Nakamura T (1992) Up-regulation of hepatocyte growth factor gene expression by interleukin-1 in human skin fibroblasts. Biochem Biophys Res Commun 188:235–243

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto K, Tajima H, Hamanoue M, Kohno S, Kinoshita T, Nakamura T (1992) Identification and characterization of “injurin,” an inducer of expression of the gene for hepatocyte growth factor. Proc Natl Acad Sci USA 89:3800–3804.

    Article  PubMed  CAS  Google Scholar 

  • Meyer SA, Jirtle RL (1989) Phenobarbital decreases hepatocyte EGF receptor expression independent of protein kinase C activation. Biochem Biophys Res Commun 158:652–659

    Article  PubMed  CAS  Google Scholar 

  • Michalopoulos G, Houck KA, Dolan ML, Luetteke NC (1984) Control of hepatocyte proliferation by two serum factors. Cancer Res 44:4414–4419

    PubMed  CAS  Google Scholar 

  • Michalopoulos GK, Appasamy R. (1993) Metabolism of HGF-SF and its role in liver regeneration. Experientia Supplementa 65:275–83.

    CAS  Google Scholar 

  • Michalopoulos G, Bowen, W, Becich M, Howard TA (1993) Comparative analysis of mitogenic and morphogenic effects of HGF and EGF on rat and human hepatocytes maintained in collagen gels. J Cell Physiol 156:443–452.

    Article  PubMed  CAS  Google Scholar 

  • Michalopoulos G, Bowen W, Mars W, Jirtle RL, Unpublished observations.

    Google Scholar 

  • Michalopoulos GK, Eckl PM, Cruise JL, Novicki DL, Jirtle RL (1987) Mechanisms of rodent liver carcinogenesis. Toxicol Ind Health 3:119–128

    PubMed  CAS  Google Scholar 

  • Mizuno K, Takehara T, Nakamura T (1992) Proteolytic activation of a single-chain precursor of hepatocyte growth factor by extracellular serine-protease. Biochem Biophys Res Commun 189:1631–1638

    Article  PubMed  CAS  Google Scholar 

  • Naka D, Ishii T, Yoshiyama Y, Miyazawa K, Hara H, Hishida T, Kidamura N (1992) Activation of hepatocyte growth factor by proteolytic conversion of a single chain form to a heterodimer. J Biol Chem 267:20114–20119

    PubMed  CAS  Google Scholar 

  • Naldini L, Tamagnone L, Vigna E, Sachs M, Hartmann G, Birchmeier W, Daikuhara Y, Tsubouchi H, Blasi F, Comoglio PM (1992) Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor. EMBO J 11:4825–4833.

    PubMed  CAS  Google Scholar 

  • Rabes HM, Wirsching R., Tuczek HV, Iseler G (1976) Analysis of cell cycle compartments of hepatocytes after partial hepatectomy. Cell Tissue Kinet 6: 517–532

    Google Scholar 

  • Rao MS Subbarao V (1986) DNA synthesis in exocrine and endocrine pancreas after partial hepatectomy in Syrian golden hamsters. Experientia 42:833–834

    Article  PubMed  CAS  Google Scholar 

  • Rifkin DB (1992) Plasminogen activator expression and matrix degradation. Matrix Suppl 1:20–22.

    PubMed  CAS  Google Scholar 

  • Roesel J, Rigsby D, Bailey A, Alvarez R, Sanchez JD, Campbell K, Shrestha K, Miller DM. (1989) Stimulation of protooncogene expression by partial hepatectomy is not tissue specific. Oncogene Research 5:129–136

    PubMed  CAS  Google Scholar 

  • Schirmacher P, Geerts A, Pietrangelo A, Dienes HP, Rogler CE. (1992) Hepatocyte growth factor/hepatopoietin A is expressed in fat-storing cells from rat liver but not myofibroblast-like cells derived from fat-storing cells. Hepatology 15:5–11.

    Article  PubMed  CAS  Google Scholar 

  • Tomiya T, Tani M, Yamada S, Hayashi S, Umeda N, Fujiwara K. (1992) Serum hepatocyte growth factor levels in hepatectomized and nonhepatectomized surgical patients. Gastroenterology 103:1621–1624.

    PubMed  CAS  Google Scholar 

  • Tsai WH, Michalopoulos GK (1991) Responsiveness of hepatocytes to epidermal growth factor, transforming growth factor-beta and norepinephrine during treatment with xenobiotic hepatic tumor promoters. Cancer Lett 57:83–90

    Article  PubMed  CAS  Google Scholar 

  • Tsai WH, Zarnegar R, Michalopoulos GK (1991) Long-term treatment with hepatic tumor promoters inhibits mitogenic responses of hepatocytes to acidic fibroblast growth factor and hepatocyte growth factor. Cancer Lett 59:103–108

    Article  PubMed  CAS  Google Scholar 

  • Wada N, Marsman DS, Popp JA (1992) Dose-related effects of the hepatocarcinogen, Wy-14,643, on peroxisomes and cell replication. Fundam Appl Toxicol 18:149–154

    Article  PubMed  CAS  Google Scholar 

  • Webber EM, Godowski PJ, Fausto N (1994) In vivo response of hepatocytes to growth factors requires an initial priming stimulus. Hepatology 489–497

    Google Scholar 

  • Wolf HK, Zarnegar R, Michalopoulos GK (1991) Localization of Hepatocyte Growth Factor in human and rat tissues: An immunohistochemical study. Hepatology 14:488–494.

    Article  PubMed  CAS  Google Scholar 

  • Yager JD, Zurlo J, Ni N (1991) Sex hormones and tumor promotion in liver. Proc Soc Exp Biol Med 198:667–674

    PubMed  CAS  Google Scholar 

  • Zarnegar R, DeFrances MC, Kost DP, Lindroos P, Michalopous GK (1991) Expression of hepatocyte growth factor mRNA in regenerating rat liver after partial hepatectomy. Biochem Biophys Res Commun 177:559–565.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pathology, Univ. of Pittsburgh Medical Center, Pittsburgh, PA, 15261, USA

    George K. Michalopoulos

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  1. George K. Michalopoulos
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Editor information

Editors and Affiliations

  1. Department of Applied Tumor Virology, Laboratory of Virus-Host Cell Interactions, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, D-69120, Heidelberg, Germany

    George G. Skouteris

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© 1994 Springer-Verlag Berlin Heidelberg

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Michalopoulos, G.K. (1994). HGF and Liver Growth Regulation. In: Skouteris, G.G. (eds) Liver Carcinogenesis. NATO ASI Series, vol 88. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79215-1_2

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  • DOI: https://doi.org/10.1007/978-3-642-79215-1_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-79217-5

  • Online ISBN: 978-3-642-79215-1

  • eBook Packages: Springer Book Archive

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