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. 1987 Jul 1;105(1):553–559. doi: 10.1083/jcb.105.1.553

Involvement of leukocyte function-associated antigen-1 (LFA-1) in the invasion of hepatocyte cultures by lymphoma and T-cell hybridoma cells

PMCID: PMC2114880  PMID: 3301869

Abstract

We studied the interaction of MB6A lymphoma and TAM2D2 T cell hybridoma cells with hepatocyte cultures as an in vitro model for in vivo liver invasion by these tumor cells. A monoclonal antibody against leukocyte function-associated antigen-1 (LFA-1) inhibited adhesion of the tumor cells to the surface of hepatocytes and consequently strongly reduced invasion. This effect was specific since control antibodies, directed against Thy.1 and against T200, of the same isotype, similar affinity, and comparable binding to these cells, did not inhibit adhesion. This suggests that LFA-1 is involved in the formation of liver metastases by lymphoma cells. TAM2D2 T cell hybridoma cells were agglutinated by anti- LFA-1, but not by control antibodies. Reduction of adhesion was not due to this agglutination since monovalent Fab fragments inhibited adhesion as well, inhibition was also seen under conditions where agglutination was minimal, and anti-LFA-1 similarly affected adhesion of MB6A lymphoma cells that were not agglutinated. The two cell types differed in LFA-1 surface density. TAM2D2 cells exhibited 400,000 surface LFA-1 molecules, 10 times more than MB6A cells. Nevertheless, the level of adhesion and the extent of inhibition by the anti-LFA-1 antibody were only slightly larger for the TAM2D2 cells.

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Selected References

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  1. Bongrand P., Pierres M., Golstein P. T cell-mediated cytolysis: on the strength of effector-target cell interaction. Eur J Immunol. 1983 May;13(5):424–429. doi: 10.1002/eji.1830130514. [DOI] [PubMed] [Google Scholar]
  2. Bross I. D., Viadana E., Pickren J. W. The metastatic spread of myeloma and leukemias in men. Virchows Arch A Pathol Anat Histol. 1975;365(2):91–101. doi: 10.1007/BF00432382. [DOI] [PubMed] [Google Scholar]
  3. Brunson K. W., Nicolson G. L. Selection and biologic properties of malignant variants of a murine lymphosarcoma. J Natl Cancer Inst. 1978 Dec;61(6):1499–1503. [PubMed] [Google Scholar]
  4. Clayberger C., Uyehara T., Hardy B., Eaton J., Karasek M., Krensky A. M. Target specificity and cell surface structures involved in the human cytolytic T lymphocyte response to endothelial cells. J Immunol. 1985 Jul;135(1):12–18. [PubMed] [Google Scholar]
  5. Davignon D., Martz E., Reynolds T., Kürzinger K., Springer T. A. Lymphocyte function-associated antigen 1 (LFA-1): a surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4535–4539. doi: 10.1073/pnas.78.7.4535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davignon D., Martz E., Reynolds T., Kürzinger K., Springer T. A. Monoclonal antibody to a novel lymphocyte function-associated antigen (LFA-1): mechanism of blockade of T lymphocyte-mediated killing and effects on other T and B lymphocyte functions. J Immunol. 1981 Aug;127(2):590–595. [PubMed] [Google Scholar]
  7. De Baetselier P., Roos E., Brys L., Remels L., Feldman M. Generation of invasive and metastatic variants of a non-metastatic T-cell lymphoma by in vivo fusion with normal host cells. Int J Cancer. 1984 Nov 15;34(5):731–738. doi: 10.1002/ijc.2910340522. [DOI] [PubMed] [Google Scholar]
  8. Dingemans K. P. Behavior of intravenously injected malignant lymphoma cells. A morphologic study. J Natl Cancer Inst. 1973 Dec;51(6):1883–1895. doi: 10.1093/jnci/51.6.1883. [DOI] [PubMed] [Google Scholar]
  9. Dustin M. L., Rothlein R., Bhan A. K., Dinarello C. A., Springer T. A. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol. 1986 Jul 1;137(1):245–254. [PubMed] [Google Scholar]
  10. Griffin J. A., Griffin F. M., Jr Augmentation of macrophage complement receptor function in vitro. I. Characterization of the cellular interactions required for the generation of a T-lymphocyte product that enhances macrophage complement receptor function. J Exp Med. 1979 Sep 19;150(3):653–675. doi: 10.1084/jem.150.3.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gromkowski S. H., Krensky A. M., Martz E., Burakoff S. J. Functional distinctions between the LFA-1, LFA-2, and LFA-3 membrane proteins on human CTL are revealed with trypsin-pretreated target cells. J Immunol. 1985 Jan;134(1):244–249. [PubMed] [Google Scholar]
  12. Haisma H. J., Hilgers J., Zurawski V. R., Jr Iodination of monoclonal antibodies for diagnosis and radiotherapy using a convenient one vial method. J Nucl Med. 1986 Dec;27(12):1890–1895. [PubMed] [Google Scholar]
  13. Hildreth J. E., August J. T. The human lymphocyte function-associated (HLFA) antigen and a related macrophage differentiation antigen (HMac-1): functional effects of subunit-specific monoclonal antibodies. J Immunol. 1985 May;134(5):3272–3280. [PubMed] [Google Scholar]
  14. Hildreth J. E., Gotch F. M., Hildreth P. D., McMichael A. J. A human lymphocyte-associated antigen involved in cell-mediated lympholysis. Eur J Immunol. 1983 Mar;13(3):202–208. doi: 10.1002/eji.1830130305. [DOI] [PubMed] [Google Scholar]
  15. Keizer G. D., Borst J., Figdor C. G., Spits H., Miedema F., Terhorst C., De Vries J. E. Biochemical and functional characteristics of the human leukocyte membrane antigen family LFA-1, Mo-1 and p150,95. Eur J Immunol. 1985 Nov;15(11):1142–1148. doi: 10.1002/eji.1830151114. [DOI] [PubMed] [Google Scholar]
  16. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  17. Martz E., Davignon D., Kürzinger K., Springer T. A. The molecular basis for cytolytic T lymphocyte function: analysis with blocking monoclonal antibodies. Adv Exp Med Biol. 1982;146:447–468. doi: 10.1007/978-1-4684-8959-0_27. [DOI] [PubMed] [Google Scholar]
  18. Martz E., Heagy W., Gromkowski S. H. The mechanism of CTL-mediated killing: monoclonal antibody analysis of the roles of killer and target-cell membrane proteins. Immunol Rev. 1983;72:73–96. doi: 10.1111/j.1600-065x.1983.tb01073.x. [DOI] [PubMed] [Google Scholar]
  19. Martz E. LFA-1 and other accessory molecules functioning in adhesions of T and B lymphocytes. Hum Immunol. 1987 Jan;18(1):3–37. doi: 10.1016/0198-8859(87)90110-8. [DOI] [PubMed] [Google Scholar]
  20. Mentzer S. J., Burakoff S. J., Faller D. V. Adhesion of T lymphocytes to human endothelial cells is regulated by the LFA-1 membrane molecule. J Cell Physiol. 1986 Feb;126(2):285–290. doi: 10.1002/jcp.1041260219. [DOI] [PubMed] [Google Scholar]
  21. Mentzer S. J., Gromkowski S. H., Krensky A. M., Burakoff S. J., Martz E. LFA-1 membrane molecule in the regulation of homotypic adhesions of human B lymphocytes. J Immunol. 1985 Jul;135(1):9–11. [PubMed] [Google Scholar]
  22. Middelkoop O. P., Roos E., Van de Pavert I. V. Infiltration of lymphosarcoma cells into hepatocyte cultures: inhibition by univalent antibodies against liver plasma membranes and lymphosarcoma cells. J Cell Sci. 1982 Aug;56:461–470. doi: 10.1242/jcs.56.1.461. [DOI] [PubMed] [Google Scholar]
  23. Miedema F., Tetteroo P. A., Hesselink W. G., Werner G., Spits H., Melief C. J. Both Fc receptors and lymphocyte-function-associated antigen 1 on human T gamma lymphocytes are required for antibody-dependent cellular cytotoxicity (killer cell activity). Eur J Immunol. 1984 Jun;14(6):518–523. doi: 10.1002/eji.1830140607. [DOI] [PubMed] [Google Scholar]
  24. Mishra G. C., Berton M. T., Oliver K. G., Krammer P. H., Uhr J. W., Vitetta E. S. A monoclonal anti-mouse LFA-1 alpha antibody mimics the biological effects of B cell stimulatory factor-1 (BSF-1). J Immunol. 1986 Sep 1;137(5):1590–1598. [PubMed] [Google Scholar]
  25. Nishizuka Y. Perspectives on the role of protein kinase C in stimulus-response coupling. J Natl Cancer Inst. 1986 Mar;76(3):363–370. [PubMed] [Google Scholar]
  26. Pierres M., Goridis C., Golstein P. Inhibition of murine T cell-mediated cytolysis and T cell proliferation by a rat monoclonal antibody immunoprecipitating two lymphoid cell surface polypeptides of 94 000 and 180 000 molecular weight. Eur J Immunol. 1982 Jan;12(1):60–69. doi: 10.1002/eji.1830120112. [DOI] [PubMed] [Google Scholar]
  27. Pircher H., Groscurth P., Baumhütter S., Aguet M., Zinkernagel R. M., Hengartner H. A monoclonal antibody against altered LFA-1 induces proliferation and lymphokine release of cloned T cells. Eur J Immunol. 1986 Feb;16(2):172–181. doi: 10.1002/eji.1830160212. [DOI] [PubMed] [Google Scholar]
  28. Roos E., Dingemans K. P., van de Pavert I. V., van den Bergh-Weerman M. Invasion of lymphosarcoma cells into the perfused mouse liver. J Natl Cancer Inst. 1977 Feb;58(2):399–407. doi: 10.1093/jnci/58.2.399. [DOI] [PubMed] [Google Scholar]
  29. Roos E., La Rivière G., Collard J. G., Stukart M. J., De Baetselier P. Invasiveness of T-cell hybridomas in vitro and their metastatic potential in vivo. Cancer Res. 1985 Dec;45(12 Pt 1):6238–6243. [PubMed] [Google Scholar]
  30. Roos E., Van de Pavert I. V. Effect of tubulin-binding agents on the infiltration of tumour cells into primary hepatocyte cultures. J Cell Sci. 1982 Jun;55:233–245. doi: 10.1242/jcs.55.1.233. [DOI] [PubMed] [Google Scholar]
  31. Roos E., Van de Pavert I. V., Middelkoop O. P. Infiltration of tumour cells into cultures of isolated hepatocytes. J Cell Sci. 1981 Feb;47:385–397. doi: 10.1242/jcs.47.1.385. [DOI] [PubMed] [Google Scholar]
  32. Roos E., van de Pavert I. V. Antigen-activated T lymphocytes infiltrate hepatocyte cultures in a manner comparable to liver-colonizing lymphosarcoma cells. Clin Exp Metastasis. 1983 Apr-Jun;1(2):173–180. doi: 10.1007/BF00121496. [DOI] [PubMed] [Google Scholar]
  33. Rosenstein M., Yron I., Kaufmann Y., Rosenberg S. A. Lymphokine-activated killer cells: lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in interleukin 2. Cancer Res. 1984 May;44(5):1946–1953. [PubMed] [Google Scholar]
  34. Rothlein R., Dustin M. L., Marlin S. D., Springer T. A. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol. 1986 Aug 15;137(4):1270–1274. [PubMed] [Google Scholar]
  35. Rothlein R., Springer T. A. The requirement for lymphocyte function-associated antigen 1 in homotypic leukocyte adhesion stimulated by phorbol ester. J Exp Med. 1986 May 1;163(5):1132–1149. doi: 10.1084/jem.163.5.1132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rousseaux J., Biserte G., Bazin H. The differential enzyme sensitivity of rat immunoglobulin G subclasses to papain and pepsin. Mol Immunol. 1980 Apr;17(4):469–482. doi: 10.1016/0161-5890(80)90087-5. [DOI] [PubMed] [Google Scholar]
  37. Sanchez-Madrid F., Nagy J. A., Robbins E., Simon P., Springer T. A. A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J Exp Med. 1983 Dec 1;158(6):1785–1803. doi: 10.1084/jem.158.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Schirrmacher V., Shantz G., Clauer K., Komitowski D., Zimmermann H. P., Lohmann-Matthes M. L. Tumor metastases and cell-mediated immunity in a model system in DBA/2 mice. I. Tumor invasiveness in vitro and metastasis formation in vivo. Int J Cancer. 1979 Feb;23(2):233–244. doi: 10.1002/ijc.2910230215. [DOI] [PubMed] [Google Scholar]
  39. Shaw S., Luce G. E., Quinones R., Gress R. E., Springer T. A., Sanders M. E. Two antigen-independent adhesion pathways used by human cytotoxic T-cell clones. Nature. 1986 Sep 18;323(6085):262–264. doi: 10.1038/323262a0. [DOI] [PubMed] [Google Scholar]
  40. Shimonkevitz R., Cerottini J. C., MacDonald H. R. Variable requirement for murine lymphocyte function-associated antigen-1 (LFA-1) in T cell-mediated lysis depending upon the tissue origin of the target cells. J Immunol. 1985 Sep;135(3):1555–1557. [PubMed] [Google Scholar]
  41. Somers S. D., Adams D. O. Enhancement of selective tumor cell binding by activated murine macrophages in response to phorbol myristate acetate. J Immunol. 1986 Mar 15;136(6):2323–2332. [PubMed] [Google Scholar]
  42. Spits H., van Schooten W., Keizer H., van Seventer G., van de Rijn M., Terhorst C., de Vries J. E. Alloantigen recognition is preceded by nonspecific adhesion of cytotoxic T cells and target cells. Science. 1986 Apr 18;232(4748):403–405. doi: 10.1126/science.3485822. [DOI] [PubMed] [Google Scholar]
  43. Springer T. A., Davignon D., Ho M. K., Kürzinger K., Martz E., Sanchez-Madrid F. LFA-1 and Lyt-2,3, molecules associated with T lymphocyte-mediated killing; and Mac-1, an LFA-1 homologue associated with complement receptor function. Immunol Rev. 1982;68:171–195. doi: 10.1111/j.1600-065x.1982.tb01064.x. [DOI] [PubMed] [Google Scholar]
  44. Strassmann G., Springer T. A., Adams D. O. Studies on antigens associated with the activation of murine mononuclear phagocytes: kinetics of and requirements for induction of lymphocyte function-associated (LFA)-1 antigen in vitro. J Immunol. 1985 Jul;135(1):147–151. [PubMed] [Google Scholar]
  45. Strassmann G., Springer T. A., Somers S. D., Adams D. O. Mechanisms of tumor cell capture by activated macrophages: evidence for involvement of lymphocyte function-associated (LFA)-1 antigen. J Immunol. 1986 Jun 1;136(11):4328–4333. [PubMed] [Google Scholar]
  46. Wallis W. J., Beatty P. G., Ochs H. D., Harlan J. M. Human monocyte adherence to cultured vascular endothelium: monoclonal antibody-defined mechanisms. J Immunol. 1985 Oct;135(4):2323–2330. [PubMed] [Google Scholar]
  47. Wright S. D., Silverstein S. C. Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes. J Exp Med. 1982 Oct 1;156(4):1149–1164. doi: 10.1084/jem.156.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. van Agthoven A., Pierres M., Goridis C. Identification of a previously unrecognized polypeptide associated with lymphocyte function associated antigen one (LFA-1). Mol Immunol. 1985 Dec;22(12):1349–1358. doi: 10.1016/0161-5890(85)90056-2. [DOI] [PubMed] [Google Scholar]

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