title: Low doses of 3-aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, stimulate angiogenesis by regulating expression of urokinase type plasminogen activator and matrix metalloprotease 2.
abstract: BACKGROUND
  Poly(ADP-Ribose) polymerase (PARP) activity has been demonstrated fundamental in many cellular processes, including DNA repair, cell proliferation and differentiation. In particular, PARP activity has been recently found to affect proliferation, migration, and tube formation of human umbilical vein endothelial cells. In recent times, PARP inhibitors have entered in clinical trials to potentiate cancer treatments by preventing DNA repair, but little is known about the effects performed by different drug concentrations on neoangiogenesis, an essential step in tumor growth.
  
  
  METHODS
  Human umbilical vein endothelial cells were treated with 3 aminobenzamide (3ABA), a PARP inhibitor, and tested for several different cellular parameters.
  
  
  RESULTS
  Here we present in vitro evidence that a low concentration of 3ABA (50 μM), stimulates angiogenesis by decreasing fibrinolytic activity, carried out by urokinase-type plasminogen activator (uPA), and by enhancing matrix metalloprotease-2 (MMP-2) gelatinolytic activity, in fibroblast growth factor-2-stimulated endothelial cells. These unbalanced pathways modify in vitro angiogenic steps, inhibiting chemoinvasion and stimulating tubulogenic activity.
  
  
  CONCLUSIONS
  Our results suggest that the proangiogenic effect of low concentrations of 3ABA alerts on the efficacy of PARP inhibitors to potentiate anticancer therapy. Moreover, they indicate that endothelial chemoinvasion and tubulogenesis depend on distinct proteolytic pathways.
authors: Department of Experimental Pathology and Oncology, University of Florence, viale G,B, Morgagni 50, 50134 Florence, Italy. marta.chevanne@unifi.it.
authors: Riccardo
authors: R
authors: Caldini
authors: Elena
authors: E
authors: Fanti
authors: Lucia
authors: L
authors: Magnelli
authors: Emanuela
authors: E
authors: Barletta
authors: Elisabetta
authors: E
authors: Tanganelli
authors: Michele
authors: M
authors: Zampieri
authors: Marta
authors: M
authors: Chevanne
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