Clinical & Experimental Metastasis

, Volume 9, Issue 2, pp 105–117 | Cite as

Interaction of B-cell hybridomas with fibroblast or hepatocyte monolayersin vitro and their metastatic behaviourin vivo

  • S. Verhaegen
  • H. Verschueren
  • J. Brissinck
  • D. Van Hecke
  • D. Dekegel
  • P. De Baetselier
Research Papers


Using anin vitro monolayer assay (MIA) we analyzed the invasive behaviour of a panel of B-cell hybridomas prepared by the fusion of non-invasive, non-metastatic NSO plasmacytoma cells and normal murine B-cells. Interaction of these hybridomas with fibroblast-like monolayers consisted mostly of adhesion on top of the monolayers, whereas only a fraction of these cells penetrated through the monolayer. This is in sharp contrast with the highly invasive properties displayed by T-cell hybridomas. Whereas T-cell hybridomas highly infiltrated monolayers of rat hepatocyrein vitro, B-cell hybridomas neither adhered to nor infiltrated hepatocyte monolayers. We found a good correlation between the degree of adhesion of B-cell hybridomas to fibroblast-like mono-layers and their metastatic capabilities upon i.v. injection into syngeneic animals. Unlike T-cell hybridomas which formed diffuse metastasis in liver and spleen, B-cell hybridomas generated nodular metastatic lessions. When normal LPS-stimulated B-lymphocytes were tested in the fibroblast-MIA, only part of the population infiltrated the monolayers. This again contrasts with T-lymphocytes where a majority of the cells penetrated through the monolayers. These results suggest that (i) B-lymphocytes express invasive properties, albeit to a lesser extent than T-lymphocytes, (ii) non-invasive B-lymphoma cells can acquire invasiveness following cell fusion with a normal B-cell, (iii) these invasive properties contribute to the malignancy of the hybridomas when tested in recipient animals.


Public Health Cancer Research Sharp Contrast Cell Fusion Anin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Abraham, D., Muir, H., andOlsen, I., 1988, Adhesion of T and B lymphocytes to fibroblasts in tissue culture.Immunology,65, 385–392.Google Scholar
  2. [2]
    Chang, T. W., Celis, E., Eisen, H. N., andSolomon, F., 1979, Crawling movements of lymphocytes on and beneath fibroblasts in culture.Proceedings of the National Academy of Sciences, USA,76, 2917–2921.Google Scholar
  3. [3]
    De Baetselier, P., Gorelik, E., Eshhar, Z., Ron, Y., Katzav, S., Feldman, M., andSegal, S., 1981, Metastatic properties conferred on nonmetastatic tumors by hybridization of spleen B-lymphocytes with plasmacytoma cells.Journal of the National Cancer Institute,67, 1079–1087.Google Scholar
  4. [4]
    De Baetselier, P., Roos, E., Brys, L., Remels, L., andFeldman, M., 1984a, Generations of invasive and metastatic variants of a non-metastatic T-cell lymphoma by in vivo fusion with normal host cells.International Journal of Cancer,34, 731–738.Google Scholar
  5. [5]
    De Baetselier, P., Roos, E., Brys, L., Remels, L., Gobert, M., Dekegel, D., Segal, S., andFeldman, M., 1984b, Nonmetastatic tumor cells acquire metastatic properties following somatic hybridization with normal cells.Cancer and Metastasis Reviews,3, 5–24.Google Scholar
  6. [6]
    De Baetselier, P., Roos, E., Verschueren, S., Verhaegen, S., Dekegel, D., Brys, L., andFeldmann, M., 1986, Acquisition of metastatic properties via somatic cells fusion: implications for tumor progressionin vivo.New Experimental Modalities in the Control of Neoplasia, edited by P. Chandra (New York: Plenum), pp. 41–55.Google Scholar
  7. [7]
    Kamenov, B., andLongenecker, B. M., 1985, Further evidence for the existence of ‘homing’ receptors on murine leukemia cells which mediate adherence to normal bone marrow stromal cells.Leukemia Research,9, 1529–1537.Google Scholar
  8. [8]
    La Rivière, G., Schipper, C. A., Collard, J. G., andRoos, E., 1988, T-cell hybridomas: correlation between invasiveness in hepatocyte and fibroblast monolayers and metastatic potential.Cancer Research,48, 3405–3410.Google Scholar
  9. [9]
    Lortan, J. E., Roobottom, C. A., Oldfield, S., andMacLennan, I. C. M., 1987, Newly produced virgin B-cells migrate to secondary lymphoid organs but their capacity to enter follicles is restricted.European Journal of Immunology,17, 1311–1316.Google Scholar
  10. [10]
    Nicolson, G. L., 1988a, Cancer metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites.Biochimica et Biophysica Acta,948, 175–224.Google Scholar
  11. [11]
    Nicolson, G. L., 1998b, Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites.Cancer and Metastasis Reviews,7, 143–188.Google Scholar
  12. [12]
    Reznikoff, C. A., Brankow, D. W., andHeidelberger, C., 1973, Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division.Cancer Research,33, 3231–3238.Google Scholar
  13. [13]
    Roos, E., La Rivière, G., Collard, J. G., Stukart, M., andDe Baetselier, P., 1985, Invasiveness of T-cell hybridomasin vitro and their metastatic potentialin vivo.Cancer Research,45, 6238–6243.Google Scholar
  14. [14]
    Roos, E., andvan de Pavert, I. V., 1982, Effect of tubulin-binding agents on the infiltration of tumor cells into primary hepatocyte cultures.Journal of Cell Science,55, 233–245.Google Scholar
  15. [15]
    Roos, E., andvan de Pavert, I. V., 1983, Antigen-activated T-lymphocytes infiltrate hepatocyte cultures in a manner comparable to liver-colonizing lymphosarcoma cells.Clinical and Experimental Metastasis,1, 173–180.Google Scholar
  16. [16]
    Roos, E., andvan de Pavert, I. V., 1987, Inhibition of lymphoma invasion and liver metastasis formation by pertussis toxin.Cancer Research,47, 5439–5444.Google Scholar
  17. [17]
    Roos, E., van de Pavert, I. V., andMiddelkoop, O. P., 1981, Infiltration of tumour cells into cultures of isolated hepatocytes.Journal of Cell Science,47, 385–397.Google Scholar
  18. [18]
    Savion, N., Vlodavsky, I., andFuks, Z., 1984, Interaction of T-lymphocytes and macrophages with cultured vascular endothelial cells: attachment, invasion, and subsequent degradation of the subendothelial extracellular matrix.Journal of Cellular Physiology,118, 169–178.Google Scholar
  19. [19]
    Schirrmacher, V., 1985, Cancer metastasis: experimental approaches, theoretical concepts, and impact for treatment strategies.Advances in Cancer Research,43, 1–73.Google Scholar
  20. [20]
    Stevens, S. K., Weissman, I. L., andButcher, E. C., 1982, Differences in the migration of B-and T-lymphocytrs: organ-selective localizationin vivo and the role of lymphocyte-endothelial cell recognition.Journal of Immunology,128, 844–851.Google Scholar
  21. [21]
    Tartakovski, B., De Baetselier, P., andSegal, S., 1980, Serological detection of H-2K and H-2D gene products. 1. Principal differences between T-and B-lymphocytes in expression of H-2D encoded alloantigens.Immunogenetics,11, 585–595.Google Scholar
  22. [22]
    Taylor, S. M., andJones, P. A., 1979, Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine.Cell,17, 771–779.Google Scholar
  23. [23]
    Van Hecke, D., Verschueren, H., andDe Baetselier, P., 1990, Identification of T-cell antigens, expressed by metastatic T-cell hybridomas and lymphomas.International Journal of Cancer,45, 773–783.Google Scholar
  24. [24]
    Verhaegen, S.,Verschueren, H.,Dekegel, D., and DeBaetselier, P., Thein vitro invasive behavior of human myelomonocytic cell lines is modulated by HuIFN-Y and pertussis toxin.Journal of Biological Response Modifiers,8, 97–107.Google Scholar
  25. [25]
    Verschaeve, L., Verschueren, H., Vanden Driessche, T., Van Hecke, D., Verhaegen, S., andDe Baetselier, P., 1989, Suggestive evidence that genes controlling invasion and metastasis of T-cell lymphomas are located on mouse chromosome 3.Genes, Chromosomes and Cancer,1, 119–130.Google Scholar
  26. [26]
    Verschueren, H., 1985, Interference reflection microscopy in cell biology: methodology and applications.Journal of Cell Science,75, 279–301.Google Scholar
  27. [27]
    Verschueren, H., Dekegel, D., andDe Baetselier, P., 1987, Development of a monolayer invasion assay for the discrimination and isolation of metastatic lymphoma cells.Invasion and Metastasis,7, 1–15.Google Scholar
  28. [28]
    Verschueren, H., De Bruyne, G. K., Dekegel, D., Mareel, M. M., andDe Baetselier, P., 1989a, The invasive behaviour of murine T-lymphoma cellsin vitro.Biomechanics of Active Movement and Deformation of Cells, edited by N. Akkas (Berlin: Springer), pp. 455–460.Google Scholar
  29. [29]
    Verschueren, H., Van Hecke, D., Hannecart-Pokorni, E., Dekegel, D., andDe Baetselier, P., 1989b, Dual effects of pertussis toxin onin vitro invasive behaviour of metastatic lymphoma variants.Clinical and Experimental Metastasis,7, 541–555.Google Scholar

Copyright information

© Rapid Communications of Oxford Ltd 1991

Authors and Affiliations

  • S. Verhaegen
    • 1
  • H. Verschueren
    • 2
  • J. Brissinck
    • 1
  • D. Van Hecke
    • 1
  • D. Dekegel
    • 2
  • P. De Baetselier
    • 1
  1. 1.Dienst Algemene Biologie, Instituut voor Moleculaire BiologieVrije Universiteit BrusselSint-Genesius-RodeBelgium
  2. 2.Pasteur Instituut van BrabantBrusselsBelgium

Personalised recommendations