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Dissimilar invasive and metastatic behavior of vincristine and doxorubicin-resistant cell lines derived from a murine T cell lymphoid leukemia

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Abstract

Multidrug resistance (MDR) lines from a murine T-cell lymphoid leukemia were selected in increasing vincristine (VCR) or doxorubicin (DOX) concentrations. Surface markers were determined by flow cytometry in both resistant (LBR-V160 and LBR-D160) and sensitive (LBR-) cell lines. Results obtained revealed similar expression of CD25, CD24, CD8, CD4, C18 and CD44, while differences in binding to hyaluronic acid (HA) were found. LBR- and LBR-D160 bound to HA only after phorbol ester (PMA) activation, while LBR-V160 failed to bind HA even after PMA treatment. Histopathological analysis disclosed that LBR-V160 was less invasive than LBR- and LBR-D160 cell lines. In vitro growth of cell lines analyzed by sulforhodamine-B uptake showed that doubling time for the three lines was 10.24 h (LBR-), 16.75 h (LBR-V160) and 16.29 h (LBR-D160). Mortality rate was determined after i.p. injection of 104 cells. Mice inoculated with LBR- died at 23 (± 2.11) days, while those inoculated with LBR-V160 or LBR-D160 died at 41 (± 9.53) or 41 (± 4.96) days, respectively. Our results demonstrated that leukemic murine T cells cultured in the long-term presence of VCR or DOX not only presented changes in the resistance phenotype but also variations in their growth and metastatic pattern.

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References

  1. Takeda Y, Nishio K, Niitani H et al. Reversal of multidrug resistance by tyrosin-kinase inhibitors in a non-P-glycoprotein-mediated multidrug-resistant cell line.Int J Cancer1994;57:229–39.

    PubMed  CAS  Google Scholar 

  2. Germann UA, Pastan I, Gottesman MM. P-glycoproteins: Mediators of multidrug resistance.Semin Cell Biol1993;4:63–70.

    Article  PubMed  CAS  Google Scholar 

  3. Berner HS, Davidson B, Berner A et al. Expression of CD44 in effusions of patients diagnosed with serous ovarian carcinoma-diagnostic and prognostic implications.Clin Exp Metastasis2000;18(2):197–202.

    Article  PubMed  CAS  Google Scholar 

  4. Gunthert U. CD44 in malignant disorders. In Gunthert U and Birchmeir W (eds): Current Topics in Microbiology and Immunology, 213/I. Attempts to Understand Metastasis Formation. Berlin/Heidelberg: Springer-Verlag1996;271–85.

    Google Scholar 

  5. Naor D, Sionov R, Ish-Shalom D. CD44: Structure, function and association with the malignant process.Adv Cancer Res1997;71: 241–319.

    Article  PubMed  CAS  Google Scholar 

  6. Screaton GR, Bell MV, Jackson DG et al. Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons.Proc Natl Acad Sci USA1992;89: 12160–4.

    Article  PubMed  CAS  Google Scholar 

  7. Guriec N, Marcellin L, Gairard B et al. CD44 exon 6 expression as a possible early prognostic factor in primary node negative breast carcinoma.Clin Exp Metastasis1996;14(5):434–9.

    Article  PubMed  CAS  Google Scholar 

  8. Kogerman P, Sy MS, Culp LA. Over-expression of human CD44s in murine 3T3 cells: Selection against during primary tumorigenesis and selection for during micrometastasis.Clin Exp Metastasis1998; 16(1):83–93.

    Article  PubMed  CAS  Google Scholar 

  9. Stauder R, Gunther U. CD44 isoforms impact on lymphocyte activation and differentiation.The Immunologist1995;3:78–83.

    CAS  Google Scholar 

  10. Toyama-Sorimachi N, Sorimachi H, Tobita Y et al.A novel ligand for CD44 is serglycin, a hematopoietic cell lineage-specific proteoglycan. J Biol Chem1995;270:7437–44.

    Article  PubMed  CAS  Google Scholar 

  11. Weber GF, Ashkar S, Glimcher MJ et al. Receptor-ligand interaction between CD44 and osteopontin (Eta-1).Science1996;271:509–12.

    PubMed  CAS  Google Scholar 

  12. Sleeman JP, Kondo K, Moll J et al. Variant exons v6 and v7 together expand the repertoire of glycosaminoglycans bound by CD44.J Biol Chem1997; 272:31837–44.

    Article  PubMed  CAS  Google Scholar 

  13. Borland G, Ross JA, Guy K.Forms and functions of CD44.Immunology 1998;93:139–48.

    Article  PubMed  CAS  Google Scholar 

  14. Catterall JB, Jones LM, Turner GA. Membrane protein glycosylaion and CD44 content in the adhesion of human ovarian cancer cells to hyaluronan. Clin Exp Metastasis1999;17(7):583–91.

    Article  PubMed  CAS  Google Scholar 

  15. Lopes EC, Scolnik M, Alvarez E et al. Modulator activity of PSC 833 and cyclosporin-A in vincristine and doxorubicin-selected multidrug resistant murine leukemic cells.Leukemia Res 2001(a); 25:85–93.

    Article  CAS  Google Scholar 

  16. Sionov RV, Naor D. Hyaluronan-independent lodgment of CD44+ lymphoma cells in lymphooid organs.Int J Cancer 1997;71:462–9.

    Article  Google Scholar 

  17. Cupis A, Pirani P, Fazzuoli L et al. Responsiveness to hormone, growth factor and drug treatment of a human breast cancer cell line: Comparison between early and late cultures.In Vitro Cell Dev Biol-Animal1998;34:836–43.

    Google Scholar 

  18. Slapak CA, Daniel JC, Levy SB. Sequential emergence of distinct resistance phenotypes in murine erythroleukemia cells under adriamycin selection: Decreased anthracycline uptake precedes increased P-glycoprotein expression.Cancer Res1990;50:7895–901.

    PubMed  CAS  Google Scholar 

  19. Lopes EC, García M, Vellón L et al. Correlation between decreased apoptosis and multidrug resistance (MDR) in murine leukemic T cell lines.Leuk Lymph2001(b); 42:775–87.

    CAS  Google Scholar 

  20. Rochman M, Moll J, Herlich P et al. CD44 receptor of lymphoma cells: Structure–function relationship and mechanism of activation. Cell Adhes Comm2000;7:331–47.

    Article  CAS  Google Scholar 

  21. Sielgeman MH, DeGrendele HC, Estess P. Activation and interaction of CD44 and hyaluronan in immunological systems.J Leukocyte Biol 1999;66:315–21.

    Google Scholar 

  22. Sanchez Lockhart M, Cabrera P, Diament M et al. Expression of CD44 splice variants in spontaneous murine tumors.Int J Mol Med2001;7: 557–62.

    Google Scholar 

  23. Lesley J, Hyman R, Kincade PW. CD44 and its interaction with extracellular matrix.Adv Immunol1993;54:271–335.

    Article  PubMed  CAS  Google Scholar 

  24. Lesley J, Hyman R. CD44 structure and fuction.Front Biosci1998; 3:616–30.

    Google Scholar 

  25. Johnson P, Maiti AM, Brown KL et al. A role for the cell adhesion molecule CD44 and sulfation in leukocyte–endothelial cell adhesion during an inflammatory response?Biochem Pharmacol2000;59: 455–65.

    Article  PubMed  CAS  Google Scholar 

  26. Stamenkovic I, Aruffo A, Amiot M et al. The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronan bearing cells.EMBO J1991;10: 343–8.

    PubMed  CAS  Google Scholar 

  27. Fabris V, Ernst G, Lopes EC et al. Chromosomes studies of murine T-cell lymphoid leukemia and derived cell lines.Cancer Gen Cytogen 2001;130:62–7.

    Article  CAS  Google Scholar 

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Lopes, E.C., Ernst, G., Aulicino, P. et al. Dissimilar invasive and metastatic behavior of vincristine and doxorubicin-resistant cell lines derived from a murine T cell lymphoid leukemia. Clin Exp Metastasis 19, 283–290 (2002). https://doi.org/10.1023/A:1015548706673

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