Dissimilar invasive and metastatic behavior of vincristine and doxorubicin-resistant cell lines derived from a murine T cell lymphoid leukemia.
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-V 160 and LBR-D 160) 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-D 160 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 10(4) 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.
Lopes
Eloisi C
EC
Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IDEHU-CONICET, Argentina. meclopes@hotmail.com
Ernst
Glenda
G
Aulicino
Paula
P
Vanzulli
Silvia
S
García
Mariana
M
Alvarez
Elida
E
Hajos
Silvia E
SE
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002455:Cell Division; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000502:physiology; D014750:Vincristine / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D014750:Vincristine; D004317:Doxorubicin; D006820:Hyaluronic Acid; D013755:Tetradecanoylphorbol Acetate