Home LiteratureArticle Details
PMID: 8878411 Published · ppublish English Journal Article

Kupffer cells and pit cells are not effective in the defense against experimentally induced colon carcinoma metastasis in rat liver.

Clinical & experimental metastasis ·Vol. 14 ·No. 4 ·1996-09-00 ·Pages 367-80

Griffini P, Smorenburg SM, Vogels IM, Tigchelaar W, Van Noorden CJ

Abstract

The present study was performed to investigate processes involved in circumvention of the immune system by advanced stages of tumor growth in the liver. The efficacy of Kupffer cells and pit cells against cancer cells was tested in vivo in an experimental model of colon carcinoma metastasis in rat liver. Liver tumors were induced by administration of CC531 colon cancer cells into the vena portae. After 3 weeks, livers were obtained and partly fixed for electron microscopic procedures or frozen in liquid nitrogen for enzyme and immunohistochemistry at the light microscope level. The activation status of Kupffer cells was studied by expression of Ia-antigen (MHC class II) and by measurement of glucose-6-phosphate dehydrogenase (G6PDH) activity in the cells in situ as a measure of production of reactive oxygen species. Large numbers of Kupffer cells were found in liver parenchyma surrounding colon carcinomas when compared with levels in control livers, but these cells were not activated. Large numbers of activated monocytes and macrophages, cytotoxic T cells but only a few pit cells were found to be recruited to the boundary between liver parenchyma and tumors or their stroma. In those areas where cancer cells invaded liver parenchyma, only newly recruited macrophages and some Kupffer cells were present but few cytotoxic T cells or pit cells were found. The low activation status of Kupffer cells both in terms of production of reactive oxygen species and Ia-antigen expression and the absence of significant numbers of pit cells at tumor sites suggest that Kupffer cells and pit cells do not play a significant role in advanced stages of tumor growth. High levels of prostaglandin E2 were detected in the parenchyma of livers containing tumors and transforming growth factor beta was detected in the stroma of the tumors, therefore suggest that cytotoxicity of newly recruited monocytes, macrophages and cytotoxic T cells may be limited in these stages because of local production of these immunosuppressive factors.

MeSH Terms
Animals Carcinoma/pathology,secondary Colonic Neoplasms/pathology Dinoprostone/analysis Disease Models, Animal Killer Cells, Natural/immunology,physiology Kupffer Cells/immunology,physiology Liver/cytology,immunology,pathology Liver Neoplasms, Experimental/secondary Macrophages/pathology Male Microscopy, Electron Monocytes/pathology Rats Rats, Inbred Strains T-Lymphocytes/pathology Transforming Growth Factor beta/analysis Tumor Cells, Cultured
Chemicals
Transforming Growth Factor beta Dinoprostone
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Griffini P
Department of Animal Biology and CNR Center for Histochemistry, University of Pavia, Italy.
Smorenburg S M
Vogels I M
Tigchelaar W
Van Noorden C J
References (75)
75 references, click to expand
  1. Statistical estimations in enzyme kinetics.
    Biochem J. 1961 Aug;80:324-32 PMID: 13785321
  2. In vivo and in vitro induction of natural killer cells by cloned human tumor necrosis factor.
    Cancer Immunol Immunother. 1988;27(2):128-32 PMID: 2458181
  3. Regulation of natural killer cell activity by transforming growth factor-beta and prostaglandin E2.
    Scand J Immunol. 1993 Jan;37(1):71-6 PMID: 8380302
  4. Tumor necrosis factor-alpha stimulates superoxide anion generation by perfused rat liver and Kupffer cells.
    Am J Physiol. 1991 Dec;261(6 Pt 1):G891-5 PMID: 1662913
  5. Interferon treatment of a transplantable rat colon adenocarcinoma: importance of tumor site.
    Int J Cancer. 1984 May 15;33(5):689-92 PMID: 6202647
  6. Experimentally induced colon cancer metastases in rat liver increase the proliferation rate and capacity for purine catabolism in liver cells.
    Histochemistry. 1993 Jul;100(1):41-51 PMID: 8226108
  7. Induction, maintenance, and reinduction of tumoricidal activity in bone marrow-derived mononuclear phagocytes by Corynebacterium parvum. Evidence for the involvement of a T cell- and interferon-gamma-independent pathway of macrophage activation.
    J Immunol. 1987 Apr 1;138(7):2366-71 PMID: 3104463
  8. Pit cells in the liver.
    Liver. 1992 Feb;12(1):3-9 PMID: 1564983
  9. Functional and morphological characterization of cultures of Kupffer cells and liver endothelial cells prepared by means of density separation in Percoll, and selective substrate adherence.
    Cell Tissue Res. 1985;241(3):639-49 PMID: 2992796
  10. Histoimmunological characterization of the cellular reaction to liver metastases induced by colon cancer cells in syngeneic rats.
    Invasion Metastasis. 1989;9(4):216-30 PMID: 2786861
  11. Liver metastasis model of colon cancer in the rat: immunohistochemical characterization.
    Invasion Metastasis. 1993;13(2):102-12 PMID: 8225852
  12. Human Kupffer cells are cytotoxic against human colon adenocarcinoma.
    Surgery. 1990 Aug;108(2):400-4; discussion 404-5 PMID: 2382233
  13. Macrophage populations in different stages of induced hepatic metastases in rats: an immunohistochemical analysis.
    Scand J Immunol. 1993 Jul;38(1):10-6 PMID: 8327856
  14. Phase II study of recombinant human tumor necrosis factor in colorectal carcinoma.
    J Biol Response Mod. 1990 Apr;9(2):247-50 PMID: 2341863
  15. Separation of Kupffer and endothelial cells of the rat liver by centrifugal elutriation.
    Exp Cell Res. 1976 May;99(2):444-9 PMID: 1269536
  16. Ex vivo activation of killer monocytes (AKM) and their application to the treatment of human cancer.
    J Clin Apher. 1988;4(2-3):118-21 PMID: 3135291
  17. alpha2-Macroglobulin is mainly produced by cancer cells and not by hepatocytes in rats with colon carcinoma metastases in liver.
    Hepatology. 1996 Mar;23(3):560-70 PMID: 8617438
  18. Superoxide release by zymosan-stimulated rat Kupffer cells in vitro.
    Eur J Biochem. 1981 Sep;119(1):171-5 PMID: 6281002
  19. Lectin-binding sites in neoplastic and non-neoplastic colonic mucosa of 1,2-dimethylhydrazine-treated rats.
    Lab Invest. 1989 Dec;61(6):670-6 PMID: 2689774
  20. Changes in the host natural killer cell population in mice during tumor development. 1. Kinetics and in vivo significance.
    Cell Immunol. 1985 Jul;93(2):250-64 PMID: 4005957
  21. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production.
    Proc Natl Acad Sci U S A. 1987 Aug;84(16):5788-92 PMID: 2886992
  22. Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients.
    Ann Surg. 1989 Oct;210(4):474-84; discussion 484-5 PMID: 2679456
  23. Enhanced secretion of prostaglandin E2 by tissue-fixed macrophages in colonic carcinoma.
    Digestion. 1990;47(3):160-6 PMID: 1964656
  24. Inhibition of macrophage Ia antigen expression by shed plasma membrane vesicles from metastatic murine melanoma lines.
    J Natl Cancer Inst. 1985 Apr;74(4):859-67 PMID: 3921747
  25. Identification of Ia glycoproteins in rat thymus and purification from rat spleen.
    Eur J Immunol. 1979 Jun;9(6):426-33 PMID: 315315
  26. Increased prostaglandin synthesis by macrophages from tumor-bearing mice.
    J Immunol. 1979 Nov;123(5):2118-25 PMID: 489975
  27. Maintenance of tumoricidal activity and susceptibility to reactivation of subpopulations of rat liver macrophages.
    J Immunother (1991). 1991 Jun;10(3):200-6 PMID: 1868044
  28. In vitro activation of murine Kupffer cells by lymphokines or endotoxins to lyse syngeneic tumor cells.
    Am J Pathol. 1984 Dec;117(3):372-9 PMID: 6391188
  29. Macrophage-mediated tumor cell killing: regulation of expression of cytolytic activity by prostaglandin E.
    J Immunol. 1981 Feb;126(2):424-7 PMID: 7451984
  30. Simultaneous localization of multiple tissue antigens using the peroxidase-labeled antibody method: a study on pituitary glands of the rat.
    J Histochem Cytochem. 1968 Sep;16(9):557-60 PMID: 5717715
  31. Analysis of enzyme reactions in situ.
    Histochem J. 1995 Feb;27(2):101-18 PMID: 7775194
  32. In situ localization of 3.2.3+ natural killer cells in tissues from normal and tumor-bearing rats.
    Cancer Res. 1991 Sep 15;51(18):4931-6 PMID: 1893382
  33. Rapid contrasting of extracellular elements in thin sections.
    Ultrastruct Pathol. 1990 Nov-Dec;14(6):519-27 PMID: 1704157
  34. Comparison between macrophage activation and enhancement of nonspecific resistance to tumors by mycobacterial immunoadjuvants.
    Proc Natl Acad Sci U S A. 1975 Oct;72(10):4105-9 PMID: 812088
  35. Influence of host defenses on the hepatic colonization of B16F10 melanoma cells.
    Clin Exp Metastasis. 1988 Mar-Apr;6(2):153-69 PMID: 3257911
  36. Elevated prostaglandin E2 production by monocytes is responsible for the depressed levels of natural killer and lymphokine-activated killer cell function in patients with breast cancer.
    Cancer. 1993 Jul 15;72(2):491-501 PMID: 8319179
  37. Analysis of metastatic spread and growth of tumor cells in mice with depressed natural killer activity by anti-asialo GM1 antibody or anticancer agents.
    J Cancer Res Clin Oncol. 1984;107(3):157-63 PMID: 6736102
  38. Prostaglandin E2 levels and lymphocyte subsets in portal venous drainage of colorectal cancers.
    Am J Surg. 1994 Feb;167(2):264-7 PMID: 8135317
  39. Identification of G6PDH-active sinusoidal cells as Kupffer cells in the rat liver.
    Cell Tissue Res. 1979 Feb 15;196(2):237-47 PMID: 421255
  40. Enzyme stimulation upon fertilization is revealed in electrically permeabilized sea urchin eggs.
    Proc Natl Acad Sci U S A. 1988 Feb;85(3):812-6 PMID: 3422463
  41. Adoptive immunotherapy of cancer using lymphokine activated killer cells and recombinant interleukin-2.
    Important Adv Oncol. 1986;:55-91 PMID: 3330541
  42. Defective natural cytotoxicity in patients with cancer: normal number of effector cells but decreased recycling capacity in patients with advanced disease.
    J Immunol. 1982 Nov;129(5):2255-9 PMID: 7119445
  43. The effect of Kupffer cell stimulation or depression on the development of liver metastases in the rat.
    Cancer Immunol Immunother. 1986;23(3):214-6 PMID: 3024833
  44. Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness.
    J Immunol. 1986 May 15;136(10):3916-20 PMID: 2871107
  45. Regulation of glucose-6-phosphate dehydrogenase activity in sea urchin eggs by reversible association with cell structural elements.
    J Cell Biol. 1986 Oct;103(4):1509-15 PMID: 3771646
  46. The role of Kupffer cells in the surveillance of tumor growth in the liver.
    J Surg Res. 1993 Aug;55(2):140-6 PMID: 8412092
  47. Practical suggestions for successful immunoenzyme double-staining experiments.
    Histochem J. 1993 Jan;25(1):1-13 PMID: 7679380
  48. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3.
    Immunology. 1985 Mar;54(3):589-99 PMID: 3882559
  49. Heterogeneity in secretory responses of rat liver macrophages of different size.
    Liver. 1995 Dec;15(6):313-9 PMID: 8609811
  50. Role of organ-associated NK cells in decreased formation of experimental metastases in lung and liver.
    J Immunol. 1985 Jun;134(6):4267-75 PMID: 3989307
  51. Liver macrophages (Kupffer cells) as cytotoxic effector cells in extracellular and intracellular cytotoxicity.
    Infect Immun. 1985 Nov;50(2):358-64 PMID: 3932206
  52. Characterization of natural cytotoxic effector cells isolated from rat liver.
    Nat Immun Cell Growth Regul. 1987;6(3):150-60 PMID: 3476847
  53. Expression and secretion of type beta transforming growth factor by activated human macrophages.
    Proc Natl Acad Sci U S A. 1987 Sep;84(17):6020-4 PMID: 2888109
  54. Effects of partial hepatectomy, phenobarbital and 3-methylcholanthrene on kinetic parameters of glucose-6-phosphate and phosphogluconate dehydrogenase in situ in periportal, intermediate and pericentral zones of rat liver lobules.
    Biochim Biophys Acta. 1995 Jan 18;1243(1):59-64 PMID: 7827108
  55. Functional characterization of liver-associated lymphocytes in patients with liver metastasis.
    Gastroenterology. 1993 Oct;105(4):1152-8 PMID: 7691673
  56. Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblastlike cells. A potential mechanism of self perpetuation in liver fibrogenesis.
    J Clin Invest. 1992 Jan;89(1):19-27 PMID: 1729271
  57. Rapid release of bound glucose-6-phosphate dehydrogenase by growth factors. Correlation with increased enzymatic activity.
    J Biol Chem. 1991 Jul 5;266(19):12442-8 PMID: 2061319
  58. The prognostic significance of natural killer cytotoxicity in patients with colorectal cancer.
    Arch Surg. 1987 Nov;122(11):1264-8 PMID: 3675190
  59. Enhancement of natural and antibody-dependent lymphocyte cytotoxicity by drugs which inhibit prostaglandin production by tumor target cells.
    Cell Immunol. 1978 Aug;39(1):154-64 PMID: 581275
  60. The autocrine production of transforming growth factor-beta 1 during lymphocyte activation. A study with a monoclonal antibody-based ELISA.
    J Immunol. 1990 Sep 1;145(5):1415-22 PMID: 2384664
  61. Reaction rate studies of glucose-6-phosphate dehydrogenase activity in sections of rat liver using four tetrazolium salts.
    Histochem J. 1985 Sep;17(9):993-1008 PMID: 4066408
  62. Kupffer cells modulate natural killer cell activity in vitro by producing prostaglandins.
    Cell Immunol. 1987 Jun;107(1):89-98 PMID: 3581176
  63. Molecular mechanisms of cancer metastasis: tumor and host properties and the role of oncogenes and suppressor genes.
    Curr Opin Oncol. 1991 Feb;3(1):75-92 PMID: 2043698
  64. Ultrastructural characteristics of human T cell clones with various cytolytic activities.
    Eur J Immunol. 1983 Aug;13(8):670-7 PMID: 6224698
  65. A new principle in polychrome staining: a system of automated staining, complementary to hematoxylin and eosin, and usable as a research tool.
    Stain Technol. 1983 Sep;58(5):245-58 PMID: 6200958
  66. In vitro activation of rat liver macrophages to tumoricidal activity by free or liposome-encapsulated muramyl dipeptide.
    Cancer Res. 1986 Sep;46(9):4330-5 PMID: 3731091
  67. In vitro inhibition of murine B-cell tumor growth by MDP, MDP(D-D) and Vaccin is mediated by macrophages.
    Int J Immunopharmacol. 1985;7(4):515-24 PMID: 3876296
  68. Chloroquine attenuates hemorrhagic shock-induced suppression of Kupffer cell antigen presentation and major histocompatibility complex class II antigen expression through blockade of tumor necrosis factor and prostaglandin release.
    Blood. 1991 Oct 1;78(7):1781-8 PMID: 1912565
  69. Enhancement of pulmonary metastases induced by decreased lung natural killer cell activity.
    J Natl Cancer Inst. 1986 Jul;77(1):99-103 PMID: 3014200
  70. Liver as a tumor cell killing organ: Kupffer cells and natural killers.
    Cancer Res. 1986 Jun;46(6):3055-60 PMID: 3009008
  71. A comparison of hepatic, splenic, peritoneal and alveolar macrophages with respect to PGE2, TXB2, production and ADCC function.
    Prostaglandins Leukot Essent Fatty Acids. 1993 Feb;48(2):149-53 PMID: 8446652
  72. Human esophageal carcinoma cell lines: prostaglandin production, biological properties, and behavior in nude mice.
    J Natl Cancer Inst. 1986 Jun;76(6):1053-6 PMID: 3458943
  73. Natural antitumor defense system of the murine liver.
    J Leukoc Biol. 1985 May;37(5):559-69 PMID: 3856617
  74. Impaired bacterial clearance and trapping in obstructive jaundice.
    Ann Surg. 1984 Jan;199(1):14-20 PMID: 6362581
  75. Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production.
    Clin Exp Metastasis. 1992 Jan;10(1):25-31 PMID: 1733644
Article Info
Journal
Clinical & experimental metastasis
Abbr.
Clin Exp Metastasis
ISSN
0262-0898
DOI
10.1007/BF00123396
Published
1996-09-00
Pages
367-80
Language
English
Region
Netherlands
NLM ID
8409970
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00123396 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2