Skip to main content
SpringerLink
Log in

Liver endothelial cells: participation in host response to lymphoma metastasis

  • Tumor Angiogenesis
  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Interactions between metastasizing tumor cells and host cells in target organs determine the outcome of metastasis. This review discusses the dual role of activated host endothelial cells in the metastatic process. On one hand, the upregulation of the expression of particular adhesion molecules leads to increased tumor cell binding, and the stimulation of angiogenesis provides the vascular support for the growth of already established metastases. On the other hand, endothelial cells can contribute to host anti-metastatic responses, e.g. by production of the cytotoxic molecule nitric oxide (NO) from arginine with the help of the inducible nitric oxide synthase (iNOS). Using a well-characterized ESbL-lacZ mouse T lymphoma model with a typical three phasic growth profile, we showed during the period of growth retardation a stimulation of NO production by ex vivo isolated liver sinusoidal endothelial cells. The induction of NO synthesis in liver endothelial cells did not require the presence of Kupffer cells and appeared to be stimulated by and dependent on mature T lymphocytes. A breakdown of this NO synthesis coincided with the second tumor expansion phase.

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

Abbreviations

IL:

interleukin

TGF:

transforming growth factor

VEGF:

vascular endothelial growth factor

PG:

prostaglandin

bFGF:

basic fibroblast growth factor

TNF:

tumor necrosis factor

ICAM-1:

intercellular adhesion molecule-1

VCAM-1:

vascular cell adhesion molecule

VLA-4:

very late activated antigen

LFA-1:

leucocyte function-associated antigen

NO:

nitric oxide

iNOS:

inducible NO synthase

NK-κB:

nuclear factor kappa B

IFN-γ:

interferon γ

CL2MBP:

dichloromethylenebisphosphonate

References

  1. Wu KK, Frasier SK, Hatzakis H: Endothelial cell function in hemostasis and thrombosis. Adv Exp Med Biol 242: 127–133, 1988

    Google Scholar 

  2. Schleef RR, Loskutoff DJ: Fibrinolytic system of vascular endothelial cells: role of plasminogen activator inhibitors. Hemostasis 18: 328–334, 1988

    Google Scholar 

  3. Grega GJ, Adamsky SW: The role of venular endothelial cells in the regulation of macromolecular permeability, microcirculation and endothelium, Lymphatics 4: 143–167, 1988

    Google Scholar 

  4. Pober JS, Collins T, Gimbrone MA, Libry P, Reiss CS: Inducible expression of class II major histocompatibility complex antigen and the immunogenicity of vascular endothelium. Transplantation 41: 141–146, 1986

    Google Scholar 

  5. Pober JS, Cotran RS: Immunologic interactions of T lymphocytes with vascular endothelium. Adv Immunol 50: 261–302, 1991

    Google Scholar 

  6. Bevilacqua MP, Pober JS, Wheeler ME, Cotran RS, Gimbrone MA: Interleukin acts on cultured human vascular endothelial cells to increase the adhesion of polymorphonuclear leucocytes, monocytes and the related cell lines. J Clin Invest 76: 2003–2011, 1985

    Google Scholar 

  7. Smedsrod B, Pertoft H, Gustafson S, Laurent T: Scavenger functions of the liver endothelial cells. Biochem J 266: 313–327, 1990

    Google Scholar 

  8. Wisse E, McCuskey RS: On the interaction of blood cells with the sinusoidal wall as observed by in vivo microsocopy of rat liver. In: Wisse E, Knook DL, McCuskey RS (eds) Cells of the hepatic sinusoid. Kupffer Cell Foundation. Leiden, The Netherlands, 1991, pp 477–482

    Google Scholar 

  9. Bogers WMJM, Stadt RK, Jansenn DJ, Van Rooijen N, Van Es LA, Dajha MR: Kupffer cell depletion in vivo results in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells. Clin Exp Immunol 86: 328–333, 1991

    Google Scholar 

  10. Jalkanen S, Bargatze R, De los Toyos J, Butcher E: Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85–95 kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells. J Cell Biol 105: 983–990, 1987

    Google Scholar 

  11. Warren RS, Yuan H, Matli MR, Gillett NA, Ferrara N: Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental Ever metastasis. J Clin Invest 95: 1789–1797, 1995

    Google Scholar 

  12. Sunderkotter C, Steinbrink K, Goebeler M, Bhardwaj R, Sorg C: Macrophages and angiogenesis. J Leukoc Biol 55: 410–422, 1994

    Google Scholar 

  13. Choi ME, Ballermann BJ: Inhibition of capillary morphogenesis and associated apoptosis by dominant negative mutant transforming growth factor-beta receptors. J Biol Chem 270: 21144–21150, 1995

    Google Scholar 

  14. Form DM, Auerbach R: Prostaglandin E2 and angiogenesis. Proc Soc Exp Biol Med 172: 214–218, 1983

    Google Scholar 

  15. Kandel J, Bossy-Wetzel E, Radvanyi F, Klagsbrun M, Folkman J, Hanahan D: Neovascularization is associated with a switch to the export of bFGF in the multistep development of fibrosarcoma. Cell 66: 1095–1104, 1991

    Google Scholar 

  16. Leibovich SJ, Polverini PJ, Shepard HM, Wiseman DM, Shively V, Nuseir N: Macrophage-induced angiogenesis is mediated by tumor necrosis factor α. Nature 329: 630–632, 1987

    Google Scholar 

  17. Folkman J, Klagsbrun M: Angiogenic factors. Science 235: 442–447, 1987

    Google Scholar 

  18. Auerbach W, Auerbach R: Angiogenesis inhibition: a review. Pharmacol Ther 63: 265–311, 1994

    Google Scholar 

  19. Tanaka T, Konno H, Matsuda I, Nakamura S, Baba S: Prevention of hepatic metastasis of human colon cancer by angiogenesis inhibitor TNP-470. Cancer Res 55: 836–839, 1995

    Google Scholar 

  20. Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature Medicine 1: 27–31, 1995

    Google Scholar 

  21. Belloni PN, Tressler RJ: Microvascular endothelial cell heterogeneity: interactions with leucocytes and tumor cells. Cancer Metastasis Rev 8: 353–389, 1990

    Google Scholar 

  22. Nicolson GL: Organ specificity of tumor metastasis: Role of preferential adhesion, invasion, and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev 7: 143–188, 1989

    Google Scholar 

  23. Auerbach R, Lu WC, Pardon E, Gumkowski F, Kaminska G, Kaminski M: Specificity of adhesion between murine tumor cells and capillary endothelium: an in vitro correlate of preferential metastasis in vivo. Cancer Res 47: 1492–1496, 1987

    Google Scholar 

  24. Pauli BU, Lee CL: Organ preference of metastasis. The role of organ-specifically modulated endothelial cells. Lab Invest 58: 379–387, 1988

    Google Scholar 

  25. Yoneda J, Saiki I, Kobayashi H, Fujii H, Ishizaki Y, Kato I, Kiso M, Hasegawa A, Azuma I: Inhibitory effect of recombinant fibronectin polypeptides on the adhesion of liver-metastatic lymphoma cells to hepatic sinusoidal endothelial cells and tumor invasion. Jpn J Cancer Res 85: 723–734, 1994

    Google Scholar 

  26. Barbera-Guillem E, Alonso-Varona A, Vidal-Vanaclocha F: Selective implantation and growth in rats and mice of experimental liver metastasis in acinar zone one. Cancer Res 49: 4003–4010, 1989

    Google Scholar 

  27. Mantovani A, Dejana E: Cytokines as communication signals between leukocytes and endothelial cells. Immunol To day 10: 370–375, 1989

    Google Scholar 

  28. Burrows FJ, Haskard DO, Hart IJ, Marshall JF, Selkirk S, Poole S, Thorpe PE: Influence of tumor-derived interleukin 1 on melanoma-endothelial cell interactions in vitro. Cancer Res 51: 4771–4775, 1990

    Google Scholar 

  29. Vidal-Vanaclocha F, Amezaga C, Asumendi A, Kaplanski G, Dinarello CA: Interleukin-1 receptor blockade reduces the number and size of murine B16 melanoma hepatic metastasis. Cancer Res 54: 2667–2672, 1994

    Google Scholar 

  30. Garofalo A, Chiviri RGS, Foglieni C, Pigott R, Mortarini R, Martin-Padura I, Anichini A, Gearing AI, Sanchez-Madrid F, Dejana E, Giavazzi R: Involvement of very late antigen 4 integrin on melanoma in interleukin 1-augmented experimental metastasis. Cancer Res 55: 414–419, 1995

    Google Scholar 

  31. Izumi Y, Taniuchi Y, Tsuji T, Smith Cw, Nakamori S, Fidler IJ, Irimura T: Characterization of human colon carcinoma variant cells selected for sialyl Lex carbohydrate antigen: liver colonization and adhesion to vascular endothelial cells. Exp Cell Res 216: 215–221, 1995

    Google Scholar 

  32. Asumendi A, Calvo F, Hernandez J-J, Alvarez A, Rocha M, Vidal-Vanacloncha F: Cancer cell surface mannose terminals and their receptors in liver and bone marrow sinusoidal endothelium contribute to B16 melanoma cell adhesion and metastasis. Lab Invest (in press), 1996

  33. Moncada S, Palmer RJ, Higgs EA: Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43: 109–134, 1991

    Google Scholar 

  34. Li L, Kilbourn RG, Adams J, Fidler IJ: Role of nitric oxide in lysis of tumor cells by cytokine-activated endothelial cells. Cancer Res 51: 2531–2535, 1991

    Google Scholar 

  35. Schmidt HHHW, Walter U: NO at work. Cell 78: 919–925, 1994

    Google Scholar 

  36. Xie Q-W, Kashiwabara Y, Nathan C: Role of transcription factor NF-kB/Rel in induction of nitric oxide synthase. J Biol Chem 269: 4705–4708, 1994

    Google Scholar 

  37. Baeuerle PA, Henkel T: Function and activation of NF-kB in the immune system. Annu Rev Immunol 12: 141–179, 1994

    Google Scholar 

  38. Stuehr DJ, Nathan CF: Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med 169: 1543–1555, 1989

    Google Scholar 

  39. Kurose I, Miura S, Fukumura D, Yonei Y, Saito H, Tada S, Suematsu M, Tsuchiya M: Nitric oxide mediates Kupffer cell-induced reduction of mitochondrial energization in hepatoma cells. A comparison with oxidative burst. Cancer Res 53: 2676–2682, 1993

    Google Scholar 

  40. Kwon NS, Stuehr DJ, Nathan CF: Inhibition of tumor cell ribonucleotide ribonuclease by macrophage-derived nitric oxide. J Exp Med 174: 761–767, 1991

    Google Scholar 

  41. Li L, Nicolson GL, Fidler IJ: Direct in vitro lysis of metastatic tumor cells by cytokine-activated murine vascular endothelial cells. Cancer Res 51: 245–254, 1991

    Google Scholar 

  42. Rocha M, Krüger A, van Rooijen N, Schirrmacher V, Umansky V: Liver endothelial cells participate in T cell dependent host resistance to lymphoma metastasis by production of nitric oxide in vivo. Int J Cancer 63: 405–411, 1995

    Google Scholar 

  43. Krüger A, Schirrmacher V, von Hoegen P: Scattered micrometastasis visualized at the single-cell level: detection and re-isolation of lacZ-labeled metastasized lymphoma cells. Int J Cancer 58: 275–284, 1994

    Google Scholar 

  44. Krüger A, Umansky V, Rocha M, Hacker HJ, Schirrmacher V, von Hoegen P: Pattern and load of spontaneous liver metastasis dependent on host immune status studied with a lacZ transduced lymphoma. Blood 84: 3166–3174, 1994

    Google Scholar 

  45. Estrada C, Gomez C, Martin C, Moncada S, Gonzalez C: Nitric oxide medites tumor necrois factor-alpha cytotoxicity in endothelial cells. Biochem Biophys Res Commun 186: 475–482, 1992

    Google Scholar 

  46. Takeshita M, Sumiyoshi Y, Masuda Y, Ohshima K, Yoshida T, Kikuchi M, Muller H: Cytokine (interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6) possessing in lymph nodes of malignant lymphoma. Pathol Res Pract 189: 18–25, 1993

    Google Scholar 

  47. Jurianz K: Molekulare Analyse der Induktion Tumorspezifische Immunantworten: Vergleich von Tumor-resistenz und Suszeptibilität in einem Maus Tumor Modellsystem. PhD Thesis, Heidelberg, 1995

  48. Nicolson GL: Cancer progression and growth: Relationship of paracrine and autocrine growth mechanisms to organ preference of metastasis. Exp Cell Res 204: 171–180, 1993

    Google Scholar 

  49. Senger DR, Perruzzi CA, Gracey CF, Papadopoulos A, Tenen DG: Secreted phosphoproteins associated with neoplastic transformation: Close homology with plasma proteins cleaved during blood coagulation. Cancer Res 48: 5770–5774, 1988

    Google Scholar 

  50. Denhardt DT, Chambers AF: Overcoming obstacles to metastasis-defenses against host defenses: Osteopontin (OPN) as a shield attack by cytotoxic host cells. J Cell Biochem 56: 1–4, 1994

    Google Scholar 

  51. Feng B, Rollo EE, Denhardt DT: Osteopontin (OPN) may facilitate metastasis by protecting cells from macrophage NO-mediated cytotoxicity: evidence from cell lines down-regulated for OPN expression by a targeted ribozyme. Clin Exp Met 13: 453–462, 1995

    Google Scholar 

  52. Bordeling RA, Murphy S: Expression of inducible nitric oxide synthase in cerebral endothelial cells is regulated by cytokine-activated astrocytes. J Neurochem 65: 1342–1347, 1995

    Google Scholar 

  53. Van Rooijen N, Sanders AM: Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Method 174: 83–93, 1994

    Google Scholar 

  54. Khazaie K, Prifti S, Beckhove P, Griesbach A, Russel s, Collins M, Schirrmacher V: Persistance of dormant tumor cells in the bone marrow of tumor cell-vaccinated mice correlates with long-term immunological protection. Proc Natl Acad Sci USA 91: 7430–7434, 1994

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Tumor Immunology Program, Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany

    Victor Umansky, Marian Rocha & Volker Schirrmacher

Authors
  1. Victor Umansky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marian Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Volker Schirrmacher
    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

Umansky, V., Rocha, M. & Schirrmacher, V. Liver endothelial cells: participation in host response to lymphoma metastasis. Cancer Metast Rev 15, 273–279 (1996). https://doi.org/10.1007/BF00437480

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00437480

Key words

Search

Navigation