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. 2013 Jul 9;17(2):100–105. doi: 10.1007/BF00200044

Natural cytotoxicity in lymphatic metastasis

I. In vitro studies using the rat tumor BSp73 and its variants

Siegfried Matzku 1,2, Hans-Peter Oberneder 1,2, Robert Keller 1,2, Margot Zöller 1,2
PMCID: PMC11039159  PMID: 6565516

Abstract

Serial transplantation of primary BSp73 ascites cells to a subcutaneous (SC) site gave rise to the appearance of two solid variants differing in their capacity to metastasize via the lymphatics. Tissue cultures derived from variant AS (nonmetastasizing) showed epithelioid morphology, while cultures derived from variant ASML (metastatic) showed spherical morphology. Upon cloning, both variants proved to be operationally homogeneous. Susceptibility of cultured BSp73 cells to NK and macrophage-mediated cytotoxicity was closely correlated to morphology, inasmuch as epithelioid cells were susceptible, while spherical cells were resistant, to lysis. With stimulated effector cells a general increase in cytotoxicity was observed, but epithelioid cells still showed a higher susceptibility level. Resistance of ASML-type cells to natural cytotoxicity was not due to the lack of recognition structures or to a general increase in the mechanical stability of spherical cells. This was concluded from cold target inhibition and from hypotonic shock treatment experiments, respectively.

Keywords: Natural Killer Cell, Effector Cell, Peritoneal Exudate Cell, Natural Cytotoxicity, Recognition Structure

References

  • 1.Acha-Orbea H, Groscurth B, Lang R, Stitz L, Hengartner H. Characterization of cloned cytotoxic lymphocytes with NK-like activity. J Immunol. 1983;130:2952. [PubMed] [Google Scholar]
  • 2.Bloom BR. Natural killers to rescue immune surveillance. Nature. 1982;300:214. doi: 10.1038/300214a0. [DOI] [PubMed] [Google Scholar]
  • 3.Brooks CG, Wayner EA, Webb PJ, Gray JD, Kenwrick S, Baldwin RW. The specificity of rat natural killer cells and cytotoxic macrophages on solid tumor-derived target cells and selected variants. J Immunol. 1981;127:2477. [PubMed] [Google Scholar]
  • 4.Dawkins JHS, Shellam GR. Augmentation of cell-mediated cytotoxicity to a rat lymphoma. II. Characterization of the non-T cytotoxic cells stimulated in vivo by tumor cells as natural killer cells. Int J Cancer. 1979;24:244. doi: 10.1002/ijc.2910240217. [DOI] [PubMed] [Google Scholar]
  • 5.Djeu JY, Huang KY, Herberman RB. Augmentation of mouse natural killer activity and induction of interferon by tumor cells in vivo. J Exp Med. 1980;151:781. doi: 10.1084/jem.151.4.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Durdik JM, Beck BN, Clark EA, Henney CS. Characterization of a lymphoma cell variant selectively resistant to natural killer cells. J Immunol. 1980;125:683. [PubMed] [Google Scholar]
  • 7.Gidlund M, Oern A, Pattengale PK, Jansson M, Wigzell H, Nilson K. Natural killer cells kill tumour cells at a given stage of differentiation. Nature. 1981;292:848. doi: 10.1038/292848a0. [DOI] [PubMed] [Google Scholar]
  • 8.Groenberg A, Kiessling R, Eriksson E, Hanson M. Variants from a MLV-induced lymphoma selected for decreased sensitivity to NK lysis. J Immunol. 1981;127:1734. [PubMed] [Google Scholar]
  • 9.Fidler IJ. General considerations for studies of experimental cancer metastasis. Methods Cancer Res. 1978;14:399. [Google Scholar]
  • 10.Hanna N. Role of natural killer cells in control of cancer metastasis. Cancer Metastasis Rev. 1982;1:45. doi: 10.1007/BF00049480. [DOI] [PubMed] [Google Scholar]
  • 11.Hanna N, Burton RC. Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastasis in vivo. J Immunol. 1981;127:1754. [PubMed] [Google Scholar]
  • 12.Hanna N, Fidler IJ. Role of natural killer cells in the destruction of circulating tumor emboli. JNCI. 1980;65:801. doi: 10.1093/jnci/65.4.801. [DOI] [PubMed] [Google Scholar]
  • 13.Hanna N, Fidler IJ. Relationship between metastatic potential and resistance to natural killer cell-mediated cytotoxicity in three murine tumor systems. JNCI. 1981;66:1183. [Google Scholar]
  • 14.Hanna N, Fidler IJ. Expression of metastatic potential of allogeneic and xenogeneic neoplasma in young nude mice. Cancer Res. 1981;41:438. [PubMed] [Google Scholar]
  • 15.Hengartner H, Acha-Orbea H, Stitz L, Rosenthal KL, Grosscurth P, Keller R. Permanently growing murine cell clones with NK-like activities. In: Herberman RB, editor. NK cells and other natural effector cells. New York: Academic Press; 1982. p. 893. [Google Scholar]
  • 16.Hisano G, Hanna N. Murine lymph node natural killer cells: Regulatory mechanisms of activation or suppression. JNCI. 1982;69:665. [PubMed] [Google Scholar]
  • 17.Hiserodt JC, Britvan LJ, Targan ST. Differential effects of various pharmacologic agents on the cytolytic reaction mechanism of the human natural killer cell lymphocyte: Further resolution of programming for lysis and KCIL into discrete stages. J Immunol. 1982;129:2266. [PubMed] [Google Scholar]
  • 18.Hudig D, Djobadze MD, Redelman D, Mendelsohn J. Active tumor cell resistance to human natural killer lymphocyte attack. Cancer Res. 1981;41:2803. [PubMed] [Google Scholar]
  • 19.Keller R. Reduced spontaneous antitumor resistance of the elderly rat is restored by Corynebacterium parvum . Br J Cancer. 1978;38:557. doi: 10.1038/bjc.1978.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Keller R. Distinctive characteristics of host tumor resistance in a rat fibrosarcoma model system. In: van Furth R, editor. Mononuclear phagocytes. Functional aspects. The Hague: Martinus Nijhoff; 1980. p. 1725. [Google Scholar]
  • 21.Keller R, Keist R. Comparison of three isotope-release assays for spontaneous cytotoxicity of macrophages. Br J Cancer. 1978;37:1078. doi: 10.1038/bjc.1978.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Keller R, Keist R. Tumor-promoting phorbol esters induced macrophage differentiation from bone marrow precursors. Exp Cell Biol. 1982;50:255. doi: 10.1159/000163154. [DOI] [PubMed] [Google Scholar]
  • 23.Kimber I, Moore M, Roberts K. Variance in resistance to natural and antibody-dependent cellular cytotoxicity and to complement-mediated lysis among K562 lines. Int J Cancer. 1983;32:219. doi: 10.1002/ijc.2910320213. [DOI] [PubMed] [Google Scholar]
  • 24.Kunkel LA, Welsh RM. Metabolic inhibitors render “resistant” target cells sensitive to natural killer cell-mediated lysis. Int J Cancer. 1981;27:73. doi: 10.1002/ijc.2910270112. [DOI] [PubMed] [Google Scholar]
  • 25.Matzku S, Komitowski D, Mildenberger M, Zöller M. Characterization of BSp73, a spontaneous rat tumor and its in vivo selected variantes showing different metastatic capacities. Invasion Metastasis. 1983;3:109. [PubMed] [Google Scholar]
  • 26.Middle JG, Embleton MJ. Immunogenicity of spontaneously arising tumours in inbred rats. Br J Cancer. 1978;38:181. [Google Scholar]
  • 27.Middle JG, Embleton MJ. Naturally arising tumors of the inbred WAB/not rat strain. II. Immunogenicity of transplanted tumors. JNCI. 1981;67:637. [PubMed] [Google Scholar]
  • 28.Olsson L, Kiger N, Kronstroem H. Sensitivity of cloned high- and low-metastatic murine Lewis tumor cells to lysis by cytotoxic autoreactive cells. Cancer Res. 1981;41:4706. [PubMed] [Google Scholar]
  • 29.Piontek GE, Groenberg A, Aehrlund-Richter L, Kiessling R, Hengartner H (1983) NK-patterned binding expressed by non-NK mouse leukocytes. Int J Cancer [DOI] [PubMed]
  • 30.Potter MR, Moore M. Organ distribution of natural cytotoxicity in the rat. Clin Exp Immunol. 1978;34:78. [PMC free article] [PubMed] [Google Scholar]
  • 31.Quan PC, Ishizaka T, Bloom BR. Studies on the mechanism of NK cell lysis. J Immunol. 1982;128:1786. [PubMed] [Google Scholar]
  • 32.Rodder JC, Kiessling R. Target-effector interaction in the natural killer cell system. Scand J Immunol. 1978;8:135. doi: 10.1111/j.1365-3083.1978.tb00505.x. [DOI] [PubMed] [Google Scholar]
  • 33.de Ruiter J, Cramer SJ, Smink T, Van Putten LM. The facilitation of tumor growth in the lung by cyclophosphamide in artificial and spontaneous metastases models. Eur J Cancer. 1979;15:1139. doi: 10.1016/0014-2964(79)90130-0. [DOI] [PubMed] [Google Scholar]
  • 34.Shellam GR, Hogg N. Gross-virus-induced lymphoma in the rat. IV. Cytotoxic cells in normal rats. Int J Cancer. 1977;19:212. doi: 10.1002/ijc.2910190211. [DOI] [PubMed] [Google Scholar]
  • 35.Tai A, Burton RC, Warner NI. Differential natural killer cell reactivity against T cell lymphomas by cells from normal or stimulated mice. J Immunol. 1980;124:1705. [PubMed] [Google Scholar]
  • 36.Talmadge JE, Meyers KM, Prieur DJ, Starkey JR. Role of NK cells in tumor growth and metastasis in beige mice. Nature. 1980;284:622. doi: 10.1038/284622a0. [DOI] [PubMed] [Google Scholar]
  • 37.Urdal DL, Kawase I, Henney CS. NK cell target interaction: Approaches towards definition of recognition structures. Cancer Metastasis Rev. 1982;1:65. doi: 10.1007/BF00049481. [DOI] [PubMed] [Google Scholar]
  • 38.Welsh RM, Zinkernagel RM. Heterospecific cytotoxic cell activity induced during the first three days of acute lymphocytic choriomeningitis virus infection. Nature. 1977;268:646. doi: 10.1038/268646a0. [DOI] [PubMed] [Google Scholar]
  • 39.Werkmeister JA, Helfand SL, Haliotis T, Ross HF, Roder JC. The effect of target cell differentiation on human natural killer cell activity: A specific defect in target cell binding and early activation events. J Immunol. 1982;129:413. [PubMed] [Google Scholar]
  • 40.Wiltrout RH, Brenda MJ, Holden HT. Variation in selectivity of human cell cytolysis by murine macrophages, macrophage-like cell lines and NK cells. Int J Cancer. 1982;30:335. doi: 10.1002/ijc.2910300313. [DOI] [PubMed] [Google Scholar]
  • 41.Wright SC, Bonavida B. YAC-1 variant clones selected for resistance to natural killer cytotoxic factors are also resistant to natural killer cell-mediated cytotoxicity. Proc Natl Acad Sci USA. 1983;80:1688. doi: 10.1073/pnas.80.6.1688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Zöller M, Matzku S. Specific cytotoxicity in vitro by T-cell-enriched lymphocyte subpopulations from rats bearing chemically induced but not spontaneous tumor. JNCI. 1980;65:1980. doi: 10.1093/jnci/65.4.769. [DOI] [PubMed] [Google Scholar]
  • 43.Zöller M, Matzku S. Characterization of natural cytotoxicity in vitro in a spontaneous rat tumor model. J Immunol. 1980;124:1683. [PubMed] [Google Scholar]
  • 44.Zöller M, Matzku S. Natural killer (NK) cells in the rat: Heterogeneity as reflection of the activation status. Immunobiology. 1983;164:27. doi: 10.1016/S0171-2985(83)80015-1. [DOI] [PubMed] [Google Scholar]
  • 45.Zöller M, Matzku S. Solid tumor-derived target cell susceptibility to macrophages and natural killer/natural cytotoxic cells in the rat. Immunobiology. 1983;164:349. doi: 10.1016/S0171-2985(83)80015-1. [DOI] [PubMed] [Google Scholar]
  • 46.Zöller M, Bellgrau D, Axberg I, Wigzell H. Natural killer cells do not belong to the recirculating lymphocyte population. Scand J Immunol. 1982;15:159. doi: 10.1111/j.1365-3083.1982.tb00634.x. [DOI] [PubMed] [Google Scholar]

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