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. 1989 May 1;108(5):1979–1985. doi: 10.1083/jcb.108.5.1979

Involvement of LFA-1 in lymphoma invasion and metastasis demonstrated with LFA-1-deficient mutants

PMCID: PMC2115560  PMID: 2654142

Abstract

Lymphocyte function-associated antigen-1 (LFA-1) is a leukocyte and lymphoma cell surface protein that promotes intercellular adhesion. We have previously shown that the invasion of hepatocyte cultures by lymphoma cells is inhibited by anti-LFA-1 antibodies (Roos, E., and F. F. Roossien. 1987. J. Cell Biol. 105:553-559). In addition, we now report that LFA-1 is also involved in invasion of lymphoma cells into fibroblast monolayers. To investigate the role of LFA-1 in metastasis of these lymphoma cells, we have generated mutants that are deficient in LFA-1 cell surface expression because of impaired synthesis of either the alpha or beta subunit precursor of LFA-1. We identified at least three distinct mutant clones. The invasive potential of the mutant cells in vitro, in both hepatocyte and fibroblast cultures, was considerably lower than that of parental cells. The metastatic potential of the mutants was much reduced, indicating that LFA-1 expression is required for efficient metastasis formation by certain lymphoma cells.

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Selected References

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  1. Anderson D. C., Springer T. A. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175–194. doi: 10.1146/annurev.me.38.020187.001135. [DOI] [PubMed] [Google Scholar]
  2. Collard J. G., Smets L. A. Effect of proteolytic inhibitors on growth and surface architecture of normal and transformed cells. Exp Cell Res. 1974 May;86(1):75–80. doi: 10.1016/0014-4827(74)90650-8. [DOI] [PubMed] [Google Scholar]
  3. Collard J. G., van de Poll M., Scheffer A., Roos E., Hopman A. H., Geurts van Kessel A. H., van Dongen J. J. Location of genes involved in invasion and metastasis on human chromosome 7. Cancer Res. 1987 Dec 15;47(24 Pt 1):6666–6670. [PubMed] [Google Scholar]
  4. 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]
  5. Ho M. K., Springer T. A. Biosynthesis and assembly of the alpha and beta subunits of Mac-1, a macrophage glycoprotein associated with complement receptor function. J Biol Chem. 1983 Mar 10;258(5):2766–2769. [PubMed] [Google Scholar]
  6. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  7. Kerbel R. S., Twiddy R. R., Robertson D. M. Induction of a tumor with greatly increased metastatic growth potential by injection of cells from a low-metastatic H-2 heterozygous tumor cell line into an H-2 incompatible parental strain. Int J Cancer. 1978 Nov 15;22(5):583–594. doi: 10.1002/ijc.2910220513. [DOI] [PubMed] [Google Scholar]
  8. Kishimoto T. K., Hollander N., Roberts T. M., Anderson D. C., Springer T. A. Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency. Cell. 1987 Jul 17;50(2):193–202. doi: 10.1016/0092-8674(87)90215-7. [DOI] [PubMed] [Google Scholar]
  9. Kishimoto T. K., O'Connor K., Lee A., Roberts T. M., Springer T. A. Cloning of the beta subunit of the leukocyte adhesion proteins: homology to an extracellular matrix receptor defines a novel supergene family. Cell. 1987 Feb 27;48(4):681–690. doi: 10.1016/0092-8674(87)90246-7. [DOI] [PubMed] [Google Scholar]
  10. Kürzinger K., Reynolds T., Germain R. N., Davignon D., Martz E., Springer T. A. A novel lymphocyte function-associated antigen (LFA-1): cellular distribution, quantitative expression, and structure. J Immunol. 1981 Aug;127(2):596–602. [PubMed] [Google Scholar]
  11. 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]
  12. Law S. K., Gagnon J., Hildreth J. E., Wells C. E., Willis A. C., Wong A. J. The primary structure of the beta-subunit of the cell surface adhesion glycoproteins LFA-1, CR3 and p150,95 and its relationship to the fibronectin receptor. EMBO J. 1987 Apr;6(4):915–919. doi: 10.1002/j.1460-2075.1987.tb04838.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Marlin S. D., Morton C. C., Anderson D. C., Springer T. A. LFA-1 immunodeficiency disease. Definition of the genetic defect and chromosomal mapping of alpha and beta subunits of the lymphocyte function-associated antigen 1 (LFA-1) by complementation in hybrid cells. J Exp Med. 1986 Sep 1;164(3):855–867. doi: 10.1084/jem.164.3.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. 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]
  17. Pals S. T., den Otter A., Miedema F., Kabel P., Keizer G. D., Scheper R. J., Meijer C. J. Evidence that leukocyte function-associated antigen-1 is involved in recirculation and homing of human lymphocytes via high endothelial venules. J Immunol. 1988 Mar 15;140(6):1851–1853. [PubMed] [Google Scholar]
  18. 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]
  19. Roos E., Roossien F. F. Involvement of leukocyte function-associated antigen-1 (LFA-1) in the invasion of hepatocyte cultures by lymphoma and T-cell hybridoma cells. J Cell Biol. 1987 Jul;105(1):553–559. doi: 10.1083/jcb.105.1.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. 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]
  23. Springer T. A., Dustin M. L., Kishimoto T. K., Marlin S. D. The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol. 1987;5:223–252. doi: 10.1146/annurev.iy.05.040187.001255. [DOI] [PubMed] [Google Scholar]
  24. Springer T. A., Thompson W. S., Miller L. J., Schmalstieg F. C., Anderson D. C. Inherited deficiency of the Mac-1, LFA-1, p150,95 glycoprotein family and its molecular basis. J Exp Med. 1984 Dec 1;160(6):1901–1918. doi: 10.1084/jem.160.6.1901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Verschueren H., Dekegel D., De Baetselier P. Development of a monolayer invasion assay for the discrimination and isolation of metastatic lymphoma cells. Invasion Metastasis. 1987;7(1):1–15. [PubMed] [Google Scholar]
  27. la Rivière G., Schipper C. A., Collard J. G., Roos E. Invasiveness in hepatocyte and fibroblast monolayers and metastatic potential of T-cell hybridomas in mice. Cancer Res. 1988 Jun 15;48(12):3405–3410. [PubMed] [Google Scholar]

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