Secretion of MMP-2 and MMP-9 induced by VEGF autocrine loop correlates with clinical features in childhood acute lymphoblastic leukemia.
In children with acute lymphoblastic leukemia (ALL), leukemic cells express several members of the VEGF family and the three VEGF receptors which, via an autocrine loop are responsible for secretion of MMP-2/-9. MMP activity and the presence of elements of the autocrine loop are correlated with clinical and prognostic parameters as follows: i) high basal MMP-9 activity with tumoral syndrome, ii) MMP-2 activity with treatment failure, iii) VEGFR-1/-3 co-expression with high hemoglobin level and iv) expression of the VEGF-A 121 isoform and favorable response to treatment. These data implicate autocrine VEGF-induced secretion of MMP-2/-9 in the physiopathology of childhood ALL.
Poyer
Florent
F
Groupe de Recherche sur le Micro-Environnement et le Renouvellement Cellulaire Intégré M.E.R.C.I., Faculté de Médecine-Pharmacie, Université de Rouen; 22 bd Gambetta, 76183 Rouen, France.
Coquerel
Bérénice
B
Pegahi
Rassa
R
Cazin
Lionel
L
Norris
Vic
V
Vannier
Jean-Pierre
JP
Lamacz
Marek
M
D000293:Adolescent; D019898:Autocrine Communication; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D012074:Remission Induction; D017211:Treatment Failure; D015275:Tumor Lysis Syndrome; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis*
D015415:Biomarkers; D006454:Hemoglobins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040321:Vascular Endothelial Growth Factor Receptor-3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9