2. Academic Validation
  3. Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis

Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis

  • Cell Metab. 2014 Jan 7;19(1):37-48. doi: 10.1016/j.cmet.2013.11.008.
Sandra Schoors 1,  Katrien De Bock 1,  Anna Rita Cantelmo 1,  Maria Georgiadou 1,  Bart Ghesquière 1,  Sandra Cauwenberghs 1,  Anna Kuchnio 1,  Brian W Wong 1,  Annelies Quaegebeur 1,  Jermaine Goveia 1,  Francesco Bifari 1,  Xingwu Wang 1,  Raquel Blanco 2,  Bieke Tembuyser 1,  Ivo Cornelissen 1,  Ann Bouché 1,  Stefan Vinckier 1,  Santiago Diaz-Moralli 3,  Holger Gerhardt 4,  Sucheta Telang 5,  Marta Cascante 3,  Jason Chesney 5,  Mieke Dewerchin 1,  Peter Carmeliet 6
Affiliations

Affiliations

  • 1 Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, Department of Oncology, University of Leuven, Leuven 3000, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven 3000, Belgium.
  • 2 Vascular Biology Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY, UK.
  • 3 Department of Biochemistry and Molecular Biology and IBUB, Universitat de Barcelona, Barcelona 08007, Spain.
  • 4 Vascular Biology Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY, UK; Vascular Patterning Laboratory, Vesalius Research Center, University of Leuven, Leuven 3000, Belgium; Vascular Patterning Laboratory, Vesalius Research Center, VIB, Leuven 3000, Belgium.
  • 5 James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
  • 6 Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, Department of Oncology, University of Leuven, Leuven 3000, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven 3000, Belgium. Electronic address: [email protected].
PMID: 24332967 DOI: 10.1016/j.cmet.2013.11.008
Abstract

Strategies targeting pathological angiogenesis have focused primarily on blocking vascular endothelial growth factor (VEGF), but resistance and insufficient efficacy limit their success, mandating alternative antiangiogenic strategies. We recently provided genetic evidence that the glycolytic activator phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) promotes vessel formation but did not explore the antiangiogenic therapeutic potential of PFKFB3 blockade. Here, we show that blockade of PFKFB3 by the small molecule 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) reduced vessel sprouting in endothelial cell (EC) spheroids, zebrafish embryos, and the postnatal mouse retina by inhibiting EC proliferation and migration. 3PO also suppressed vascular hyperbranching induced by inhibition of Notch or VEGF receptor 1 (VEGFR1/Flt-1) and amplified the antiangiogenic effect of VEGF blockade. Although 3PO reduced glycolysis only partially and transiently in vivo, this sufficed to decrease pathological neovascularization in ocular and inflammatory models. These insights may offer therapeutic antiangiogenic opportunities.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-19824
    99.56%, PFKFB3 Blocker