Skip to main content
SpringerLink
Log in

An electron microscopy study of Kupffer cells in livers of mice having Friend erythroleukemia hepatic metastases

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Kupffer cells, which are part of the reticuloendothelial system, play an important role in clearing pathogenic substances, including tumor cells, from the liver. The role of Kupffer cells in tumor development is very important as Kupffer cells can be manipulated to a tumoricidal state with biological response modifiers to kill tumor cells and thus to decrease tumor burden and extend survival time. To gain additional information on the role of Kupffer cells and their interaction with tumor cells in hepatic metastases, we studied an established experimental hematogenous metastatic model (Friend erythroleukemia) in mouse livers by light and electron microscopy. Highly activated Kupffer cells were observed in close contact with tumor cells in sinusoids and also in tumor forming foci within the hepatic parenchyma. The Kupffer cells were activated by the presence of the hematogenous tumor cells and were able to lyse and phagocytose them. However, some tumor cells evaded the Kupffer cells as metastases still occurred. Kupffer cells and other macrophages were found to leave the sinusoids and migrate to sites of potential tumor development where they interacted with tumor cells and intimately wrapped their processes around fat storing cells. It is possible that these macrophages which cross biological barriers could be used to deliver drug-loaded microparticles (liposomes and microcapsules) to tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Roos E, Dingemans IP, Van DePavert IV and Van Den Bergh-Weerman MA, 1978, Mammary carcinoma cells in mouse liver: infiltration of liver tissue and interaction with Kupffer cells.Br J Cancer,38, 88–99.

    Google Scholar 

  2. Roos E, Tulp A, Middelkoop OP and Van DePavert IV, 1982, Interaction between liver-metastasizing lymphoid tumor cells and hepatic sinusoidal endothelial cells. In: Knook DL, Wisse E, eds.Sinusoidal Liver Cells. Amsterdam: Elsevier Biomedical Press, pp. 147–54.

    Google Scholar 

  3. Strauli P and Haemmerli G, 1984, The role of cancer cell motility in invasion.Cancer Metastasis Rev,3, 127–41.

    Google Scholar 

  4. Kawaguchi T and Nakamura K, 1986, Analysis of the lodgement and extravasation of tumor cells in experimental models of hematogenous metastasis.Cancer Metastasis Rev,5, 77–94.

    Google Scholar 

  5. Nicholson G, 1989, Metastatic tumor cell interaction with endothelium basement membrane and tissue.Curr Opin Cell Biol,1, 1009–19.

    Google Scholar 

  6. Phillips NC, 1989, Kupffer cells and liver metastases.Cancer Metastasis Rev,8, 231–52.

    Google Scholar 

  7. Phillips NC and Tsao MS, 1989, Inhibition of experimental liver tumor growth in mice by liposomes containing a lipophilic muramyl dipeptide derivative.Cancer Res,49, 936–9.

    Google Scholar 

  8. Fidler IJ. Macrophage therapy of cancer metastasis, 1988, In:Metastasis (Ciba Foundation Symposium). Chichester: John Wiley & Sons, pp. 211–22.

    Google Scholar 

  9. Fidler IJ. The use of liposomes as drug carriers in the immunotherapy of cancer, 1989, In: Roerdink FHD, Kroon AM, eds.Drug Carrier Systems. New York: John Wiley and Sons, pp. 213–48.

    Google Scholar 

  10. Fidler IJ, 1992, Systemic macrophage activation with liposome-entrapped immunomodulators for therapy of cancer metastasis.Res Immunol,143, 199–204.

    Google Scholar 

  11. Roh MS, Kahky MP, Oyedeji C,et al. 1992, Murine Kupffer cells and hepatic natural killer cells regulate tumor growth in a quantitative model of colorectal liver metastases.Clin Exp Metastasis,10, 317–27.

    Google Scholar 

  12. Roh MS, Wang L, Oydeji C,et al. 1990, Human Kupffer cells are cytotoxic against human colon adenocarcinoma.Surgery,108, 400–5.

    Google Scholar 

  13. Xu ZL, Bucana CD and Fidler IJ, 1984,In vitro activation of murine Kupffer cells by lymphokines or endotoxins to lyse syngeneic tumor cells.Am J Pathol,117, 372–9.

    Google Scholar 

  14. Adachi Y, Shigeki A, Funaki N,et al. 1992, Tumoricidal activity of Kupffer cells augmented by anticancer drugs.Life Sci,5, 177–83.

    Google Scholar 

  15. Fidler IJ and Schroit AJ, 1988, Recognition and destruction of neoplastic cells by activated macrophages: discrimination of altered self.Biochem Biophys Acta,948, 151–73.

    Google Scholar 

  16. Gardner CR, Wasserman AJ and Laskin DL, 1991, Liver macrophage-mediated cytotoxicity towards mastocytoma cells involves phagocytosis of tumor targets.Hepatology,14, 318–24.

    Google Scholar 

  17. Jack EM, 1990, Ultrastructural changes in chemically induced preneoplastic focal lesions in the rat liver: stereological study.Carcinogenesis,11, 1531–8.

    Google Scholar 

  18. Jánossy L, Zalatnai A and Lapis K, 1986, Quantitative light microscopic study on the distribution of Kupffer cells during chemical hepatocarcinogenesis in the rat.Carcinogenesis,7, 1365–9.

    Google Scholar 

  19. Bouwens L, 1988, Structural and functional aspects of Kupffer cells.Revisiones Sobre Biologia Cellular,16, 69–98.

    Google Scholar 

  20. Fidler IJ, 1992, Therapy of disseminated melanoma by liposome-activated macrophages.World J Surg,16, 270–6.

    Google Scholar 

  21. Gresser I, Maury C and Belardelli F, 1987, Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant friend leukemia cells VI. Adjuvant therapy after surgery in the inhibition of liver and spleen metastases.Int J Cancer,39, 789–92.

    Google Scholar 

  22. Gresser I, Maury C, Woodrow D,et al. 1988, Interferon treatment markedly inhibits the development of tumor metastases in the liver and spleen and increases survival time of mice after intravenous inoculation of Friend erythroleukemia cells.Int J Cancer,41, 135–42.

    Google Scholar 

  23. Saiki I and Fidler IJ, 1985, Synergistic activation by recombinant mouse interferon-gamma and muramyl dipeptide tumoricidal properties in mouse macrophages.J. Immunol,35, 684–8.

    Google Scholar 

  24. Hoedemakers RNMJ, Daemen T and Scherphof GL, 1991, Tumor cytolytic activity and TNF secretion of the rat liver macrophage population after intravenous administration of liposome-encapsulated MDP. In: Wisse E, Knook DL, McCuskey RS, eds.Cells of the Hepatic Sinusoid. Leiden, The Netherlands: Kupffer Cell Foundation, Vol 3, pp. 319–23.

    Google Scholar 

  25. Wisse E, de Wilde A and de Zanger R, 1984, Perfusion fixation of human and rat liver issue for light and electron microscopy: A review and assessment of existing methods with special emphasis on sinusoidal cells and microcirculation. In: Revel JP, Haggis GH, eds. Science of Biological Specimen Preparation. Chicago, IL, USA: SEM, pp. 31–8.

    Google Scholar 

  26. Ledingham JM and Simpson FO, 1970, Intensification of osmium staining by p-phenylenediamine: Paraffin and epon embedding; lipid granules in renal medulla.Stain Technol,45, 255–60.

    Google Scholar 

  27. Barberá-Guillem E, Alonso-Varona A and Vidal-Vanaclocha F, 1989, Selective implantation and growth in rats and mice of experimental liver metastasis in acinar zone one.Cancer Res,49, 4003–10.

    Google Scholar 

  28. Vidal-Vanaclocha F, Alonso-Varona A, Ayala R and Barberá-Guillem E, 1990, Functional variations in liver tissue during the implantation process of metastatic tumor cells.Virchows Archiv A Pathol Anat Histopathol,416, 189–95.

    Google Scholar 

  29. Kan Z, Ivancev K, Lunderquist A,et al. 1993,In vivo microscopy of hepatic tumors in animal models: a dynamic investigation of blood supply to hepatic metastases.Radiol,187, 621–6.

    Google Scholar 

  30. Weiss L, 1990, Metastatic inefficiency.Adv Cancer Res,54, 159–211.

    Google Scholar 

  31. Weiss L, Nannmark U, Johansson BR and Bagge U, 1992, Lethal deformation of cancer cells in the microcirculation: A potential rate regulator of hematogenous metastasis.Int J Cancer,50, 103–7.

    Google Scholar 

  32. Dingemans KP, 1988, B16 Metastases in mouse liver and lung. II Morphology.Inv Metastasis 8, 87–102.

    Google Scholar 

  33. Adkins KF, Martinez MG and Hartley MW, 1969, Ultrastructure of giant-cell lesions.Oral Surg, Oral Med, Oral Path,28, 713–23.

    Google Scholar 

  34. Ramadori G, 1991, The stellate cell (Ito-cell, fatstoring cell, lipocyte, perisinusoidal cell) of the liver.Virchows Arch B Cell Pathol,61 147–58.

    Google Scholar 

  35. Ichida T, Hata K, Yamada S,et al. 1990, Subcellular abnormalities of liver sinusoidal lesions in human hepatocellular carcinoma.J Submicroscopic Cytol Pathol,22, 221–9.

    Google Scholar 

  36. Bioulac-Sage P, Lafon ME, LeBail B,et al. 1988, Ultrastructure of sinusoids in liver disease. In: Bioulac-Sage P, Balabaud C, eds.Sinusoids in Human Liver: Health and Disease, Rijswijk, The Netherlands: Kupffer Cell Foundation, pp. 223–78.

    Google Scholar 

  37. Chung LWK, 1991, Fibroblasts are critical determinants in prostatic cancer growth and dissemination.Cancer Met Rev,10, 263–74.

    Google Scholar 

  38. Eccles SA, 1974, Macrophage content of tumours in relation to metastatic spread of host immune reactionNature,250, 667–9.

    Google Scholar 

  39. Decker K, 1989, Hepatic mediators of inflammation in cells of the hepatic sinusoid. In: Wisse E, Knook DL, Decker K, eds.Cells of the Hepatic Sinusoid. Vol 2. Rijswijk, The Netherlands: Kupffer Cell Foundation, pp. 171–5.

    Google Scholar 

  40. Decker K, 1990, Biologically active products of stimulated liver macrophages (Kupffer cells).Eur J Biochem,192, 245–61.

    Google Scholar 

  41. Manifold IH, Triger DR and Underwood JCE, 1983, Kupffer-cell depletion in chronic liver disease: implications for hepatic carcinogenesis.Lancet,2, 431–3.

    Google Scholar 

  42. Kleinerman ES, Maeda M and Jaffe N, 1993, Liposome-encapsulated muramyl tripeptide: a new biologic response modifier for the treatment of osteosarcoma.Cancer Treat Res,62, 101–7.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Diagnostic Radiology, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 057, 77030, Houston, TX, USA

    Patricia A. McCuskey, Zuxing Kan & Sidney Wallace

Authors
  1. Patricia A. McCuskey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zuxing Kan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sidney Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

McCuskey, P.A., Kan, Z. & Wallace, S. An electron microscopy study of Kupffer cells in livers of mice having Friend erythroleukemia hepatic metastases. Clin Exp Metast 12, 416–426 (1994). https://doi.org/10.1007/BF01755885

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01755885

Keywords

Search

Navigation