Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Immunologic enhancement of experimental metastasis in the rat

  • 13 Accesses

  • 1 Citations

Summary

Using a series of immunologically cross-reactive metastatic tumor variants, we demonstrate that serum from animals bearing pulmonary tumor colonies possesses enhancing properties in the experimental metastasis (lung colony) assay. Enhancement is produced by chronic serum administration and promotes the growth of tumor cells arrested in the lungs which would not otherwise proliferate to form grossly detectable lung nodules. Tumor-bearer serum from animals with lung colonies derived from the most highly metastatic variant examined is shown to possess enhancing properties in both BD-IX(H-1d) and BD-IV(H-1d) rat strains, while tumor-bearer serum from animals with lung colonies derived from the less metastatic parent tumor cell line possesses enhancing properties in the BD-IX rat strain only. Removal of immunoglobulin from enhancing serum by affinity column chromatography simultaneously removes the enhancing factor(s), and enhancing activity correlates with the presence of increased levels of Clq-binding immune complexes in the serum. Serum levels of immune complexes are shown to be more elevated in serum from animals bearing lung colonies derived from the most highly metastatic variant. The enhancing moieties are shown to bind to concanavalin A, but not to staphylococcal protein A, and the active fraction elutes from concanavalin A-Sepharose with α-methyl-mannoside. Consideration of immunoprecipitation studies on whole and fractionated enhancing sera, along with studies on affinity purified isotype fractions reveals that the activity resides with antibodies of IgG2b subclass.

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

References

  1. 1.

    Amlot PL, Pussell B, Slaney JM, Williams BD (1978) Correlations between immune complexes and prognostic factors in Hodgkin's disease. Clin Exp Immunol 31:166

  2. 2.

    Badger AM, Cooperband SR, Merluzzi VJ, Glasgow AH (1977) Immunosuppressive activity of ascitic fluid from patients with cancer metastatic to the peritoneum. Cancer Res 37:1220

  3. 3.

    Baldwin RW (1981) Mechanisms of immunity in cancer. Pathobiol Annu 11:155

  4. 4.

    Bansal SC, Bansal BR, Boland JP (1976) Blocking and unblocking serum factors in neoplasia. Curr Top Microbiol Immunol 75:45

  5. 5.

    Bansal SC, Bansal BR, Thomas HL, Siegel PD, Rhoads Jr. JE, Cooper DR, Terman DS, Mark R (1978) Ex vivo removal of serum IgG in a patient with colon carcinoma. Cancer 40:1

  6. 6.

    Basombrio MA, Prehn RT (1972) Immune status of autochthonous and adoptively protected mice towards spontaneous and chemically induced tumors. Cancer Res 32:2545

  7. 7.

    Benca R, Quintans J, Kearney JF, Flood PM, Schreiber H (1980) Studies on phosphorylcholine-specific T cell idiotypes and idiotype-specific immunity. Mol Immunol 17:823

  8. 8.

    Beverley PCL (1982) Antibodies and cancer therapy. Nature 297:358

  9. 9.

    Carpentier NA, Lange GT, Fiere D, Fournie GD, Lambert PH, Miescher PA (1977) Clinical relevance of circulating immune complexes in human leukemia. J Clin Invest 60:874

  10. 10.

    Day NK, O'Reilly-Felice C, Hardy Jr. WD, Good RA, Witkin SS (1980) Circulating immune complexes associated with naturally occurring lymphosarcoma in pet cats. J Immunol 126:2363

  11. 11.

    Duc HT, Kinsky RG, Voisin GA (1982) Passive allograft enhancement by subclasses of polyclonal antibodies directed toward restricted regions of the major histocompatibility complex. Transplantation 33:492

  12. 12.

    Eiras AS, Robins RA, Baldwin RW, Byers VS (1980) Circulating immune complexes in patients with bone tumours. Int J Cancer 25:735

  13. 13.

    Fidler IJ, Gersten DM, Budmen MB (1976) Characterization in vivo and in vitro of tumor cells selected for resistance to syngeneic lymphocyte-mediated cytotoxicity. Cancer Res 36:3160

  14. 14.

    Flood PM, Kripke ML, Rowley DA, Schreiber H (1980) Suppression of tumor rejection by autologous anti-idiotypic immunity. Proc Natl Acad Sci USA 77:2209

  15. 15.

    Gordon BR, Moroff S, Hurvitz AI, Matus RE, McEwen EG, Good RA, Day NK (1980) Circulating immune complexes in sera of dogs with benign and malignant breast disease. Cancer Res 40:3627

  16. 16.

    Gorelik E, Segal S, Feldman M (1980) Control of lung metastasis progression in mice: role of growth kinetics of 3LL Lewis lung carcinoma and host immune status. JNCI 65:1257

  17. 17.

    Gorelik E, Wiltrout RH, Brunda MJ, Holden HT, Herberman RB (1982) Augmentation of metastasis formation by thioglycollate-elicited macrophages. Int J Cancer 29:575

  18. 18.

    Harris TN, Harris SH (1978) Suppression of growth of a mouse plasmacytoma by the IgG2 fraction of syngeneic anti-tumor globulin. J Reticuloendothel Soc 23:351

  19. 19.

    Harris TN, Harris SH, Henri EM, Farber MB (1980) Enhancement of growth of allogeneic mouse tumor by the IgG1 fraction of alloantibody preparations. JNCI 60:167

  20. 20.

    Heimer R, Vaux Saint Cyr C de (1979) Circulating immune complexes in sera of hamsters bearing Simian virus 40-induced tumors. Cancer Res 39:2919

  21. 21.

    Hellstrom KE, Hellstrom I (1979) Enhancement of tumor outgrowth by tumor associated blocking factors. Int J Cancer 23:366

  22. 22.

    Hellstrom KE, Hellstrom I, Nepom JT (1977) Specific blocking factors — are they improtant? Biochim Biophys Acta 473:121

  23. 23.

    Herlyn D, Koprowski H (1982) IgG2a monoclonal antibodies inhibit human tumor growth through interaction with effector cells. Proc Natl Acad Sci USA 79:4761

  24. 24.

    Höffken K, Meredith ID, Robins RA, Baldwin RW, Davies CJ, Blamey RW (1978a) Immune complexes and prognosis of human breast cancer. Lancet I:672

  25. 25.

    Höffken K, Price MR, McLaughlin P, Moore VE, Baldwin RW (1978b) Circulating immune complexes in rats bearing chemically induced tumors. I. Sequential determination during the growth of tumors at various body sites. Int J Cancer 21:496

  26. 26.

    Höffken K, Price MR, Moore VE, Baldwin RW (1978c) Circulating immune complexes in rats bearing chemically induced tumors. II. Characterization of sera from different stages of tumor growth. Int J Cancer 22:576

  27. 27.

    Holohan TV, Phillips TM, Bowles C, Deisseroth A (1982) Regression of canine mammary carcinoma after immunoadsorption therapy. Cancer Res 42:3663

  28. 28.

    Isakov N, Feldman M, Segal S (1981) Control of progression of local tumor and pulmonary metastasis of the 3LL Lewis lung carcinoma by different histocompatibility requirements in mice. JNCI 66:919

  29. 29.

    Jerne NK (1974) Towards a network theory of the immune system. Ann Immunol (Paris) 125C:373

  30. 30.

    Johnson RJ, Pasternak GR, Shin HS (1977a) Antibody-mediated suppression of tumor growth. I. Suppression by murine IgG1 isolated from alloantiserum. J Immunol 118:489

  31. 31.

    Johnson RJ, Pasternak GR, Shin HS (1977b) Antibody-mediated suppression of tumor growth. II. Macrophage and platelet cooperation with murine IgG1 isolated from alloantiserum. J Immunol 118:494

  32. 32.

    Johnson RJ, Pasternak GR, Drysdale BE, Shin HS (1977c) Antibody mediated suppression of tumor growth. III. Molecular assay of murine IgG1 alloantibody required to cause tumor suppression in vivo. J Immunol 118:498

  33. 33.

    Jones FR, Yoshida LH, Ladiges WC, Kenny MA (1980) Treatment of feline leukemia and reversal of FeLV by ex vivo removal of IgG: a preliminary report. Cancer 46:675

  34. 34.

    Klaus GGB (1978) Antigen-antibody complexes elicit anti-idiotypes. Nature 272:265

  35. 35.

    Laurell C (1972) Electroimmunoassay. Scand J Clin Invest 29:21

  36. 36.

    McDonald TL (1981) Isolation of immune complexes by an equine Clq-like factor. Immunol Commun 10:741

  37. 37.

    McDonald TL (1982) Isolation of Clq-binding virus-antibody immune complexes from lactic dehydrogenase virus (LDV)-infected mice. Immunology 45:365

  38. 38.

    Medgyesi GA, Fust G, Gergely J, Bazin H (1978) Classes and subclasses of rat immunoglobulins; interactions with the complement system and with staphylococcal protein A. Immunochemistry 15:125

  39. 39.

    Medgyesi GA, Miklos K, Kulics J, Fust G, Gergely J, Bazin H (1981) Classes and subclasses of rat antibodies: reaction with the antigen and interaction of the complex with the complement system. Immunology 43:171

  40. 40.

    Mullen Y, Raison R, Hildemann W (1977) Cytotoxic versus immunoblocking effects of specific alloantibodies. Transplantation 24:99

  41. 41.

    Ray PK, Idicalla A, Mark R, Thoads JE, Thomas H, Bassett JG, Cooper DR (1982) Extracorporeal immunoadsorption of plasma from a metastatic colon carcinoma by a protein A-containing nonviable Staphylococcus aureus. Cancer 49:1800

  42. 42.

    Ristow SS, Rossen RD, Fryd DS, McKhann CF (1979) Circulating immune complexes in colon cancer patient sera. Cancer 43:1320

  43. 43.

    Ron Y, Gorelik E, Feldman M, Segal S (1982) Effect of splenectomy progression of postoperative pulmonary metastases of the 3LL tumor. Eur J Cancer Clin Oncol 18:391

  44. 44.

    Rossen RD, Reisberg MA, Hersh EM, Gutterman JU (1977) The Clq binding test for soluble immune complexes: clinical correlations obtained in patients with cancer. J Natl Cancer Inst 58:1205

  45. 45.

    Starkey JR, Davis WC, Talmadge JE (1982) Immunoselection of tumor variants resistant to antibody-mediated cytotoxicity: their immunologic and metastatic characterization. Cancer Immunol Immunother 14:124

  46. 46.

    Steele Jr G, Ankerst J, Sjögren HO (1974) Alteration of in vitro antitumor activity of tumor-bearer sera by absorption with Staphylococcus aureus, Cowan I. Int J Cancer 14:83

  47. 47.

    Steplewski Z, Lubeck MD, Koprowski H (1983) Human macrophages armed with murine immunoglobulin G2a antibodies to tumors destroys human cancer cells. Science 221:865

  48. 48.

    Talmadge JE, Starkey JR, Davis WC, Cohen WL (1979) Introduction of metastatic heterogeneity by short-term in vivo passage of a cloned transformed cell line. Journal of Supramolecular Structure 12:227

  49. 49.

    Talmadge JE, Starkey JR, Stanford DR (1981) In vitro characteristics of metastatic variant subclones of restricted genetic origin. Journal of Supramolecular Structure and Cellular Biochemistry 15:139

  50. 50.

    Terman DS, Yamamoto T, Mattioli GC, Tillquist R, Henry J, Poser R, Daskal Y (1980a) Extensive necrosis of spontaneous canine mammary adenocarcinoma after extracorporeal perfusion over Staphylococcus aureus, Cowans 1. I. Description of acute tumoricidal response: morphologic, histologic, immunohistochemical, immunologic, and serologic findings. J Immunol 124:795

  51. 51.

    Terman DS, Young JB, Shearer WT, et al. (1980b) Preliminary observations of the effects on breast adenocarcinoma of plasma perfused over immobilized protein A. N Engl J Med 305:1195

  52. 52.

    Voisin GA (1980) Role of antibody classes in the regulatory facilitation reaction. Immunol Rev 49:3

  53. 53.

    Waal R de, Cornelissen I, Capel P, Koene R (1979) Passive enhancement of mouse tumor allografts by alloantibodies in Fc-dependent. J Immunol 123:1353

  54. 54.

    Yamamoto H, Katz DH (1980) Biological effects of anti-idiotypic antibodies on lymphocyte function. Cell Immunol 50:369

Download references

Author information

Correspondence to Jean R. Starkey.

Additional information

Abbreviations used: NK, natural killer cell; CIC, circulating immune complex; RhC, rheumatoid-Clq protein complex; Ig, immunoglobulin

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Starkey, J.R., Ristow, S.S., McDonald, T.L. et al. Immunologic enhancement of experimental metastasis in the rat. Cancer Immunol Immunother 17, 42–50 (1984). https://doi.org/10.1007/BF00205496

Download citation

Keywords

  • Concanavalin
  • Lung Nodule
  • Experimental Metastasis
  • Fraction Elute
  • Tumor Variant