@Article{,
AUTHOR = {Rassa Pegahi, Florent Poyer, Elisabeth Legrand, Lionel Cazin, Jean-Pierre Vannier, Marek Lamacz},
TITLE = {Spontaneous and cytokine-evoked production of matrix metalloproteinases by bone marrow and peripheral blood pre-B cells in childhood acute lymphoblastic leukaemia},
JOURNAL = {European Cytokine Network},
VOLUME = {16},
YEAR = {2005},
NUMBER = {3},
PAGES = {223--232},
URL = {http://www.techscience.com/ECN/v16n3/66218},
ISSN = {1952-4005},
ABSTRACT = {The present work focused on the study of the secretory activity of pre-B acute lymphoblastic
leukaemia (ALL) cells harvested from bone marrow (BM) and peripheral blood (PB) in 16 children. The basal and
cytokine (SDF-1, GM-CSF, bFGF, VEGF)-stimulated secretions of gelatinases 2 and 9 (MMPs-2 and -9) and
expression of their genes were monitored by zymography and RT-PCR, respectively. A wide heterogeneity was
found in the secretory capacities of these cells. The basal secretion of MMP-9 was more frequently observed than
that of MMP-2 in both cell types. The cytokines VEGF and bFGF were found to induce predominant stimulatory
effects on the MMP-2 secretion. In contrast, GM-CSF was shown to exert a more pronounced activation of the
MMP-9 production. Experiments using inhibitors of metabolic pathways (U0126, LY294002 and SN50) revealed
that the secretion of MMP-9 was mediated through PI3/MEK1 kinases. The MMP-2 secretion appeared to be
however, stimulated through a different metabolic pathway. The microfluorimetric approach showed that the
basal and stimulated secretions of MMPs-2 and -9 depended on the extracellular calcium pool. The cytokines
VEGF and bFGF represent potent factors increasing the intracellular calcium concentration with similar kinetics.
In contrast, GM-CSF was found to activate a verapamil-sensitive efflux of indo-1 from cytosol suggesting that this
cytokine could be responsible for the activation of xenobiotic membrane transporters. Experiments using the
trypan blue exclusion test demonstrated that bFGF, in contrast to VEGF and GM-CSF, markedly augmented
pre-B ALL cell survival Further investigations into a possible correlation between the plasma concentrations of
MMP-2 and -9, VEGF, bFGF and GM-CSF, and the poor evolution of pre-B ALL in children could have valuable
diagnostic implications.},
DOI = {}
}