title: Incomplete and transitory decrease of glycolysis: a new paradigm for anti-angiogenic therapy?
abstract: During vessel sprouting, a migratory endothelial tip cell guides the sprout, while proliferating stalk cells elongate the branch. Tip and stalk cell phenotypes are not genetically predetermined fates, but are dynamically interchangeable to ensure that the fittest endothelial cell (EC) leads the vessel sprout. ECs increase glycolysis when forming new blood vessels. Genetic deficiency of the glycolytic activator PFKFB3 in ECs reduces vascular sprouting by impairing migration of tip cells and proliferation of stalk cells. PFKFB3-driven glycolysis promotes the tip cell phenotype during vessel sprouting, since PFKFB3 overexpression overrules the pro-stalk activity of Notch signaling. Furthermore, PFKFB3-deficient ECs cannot compete with wild-type neighbors to form new blood vessels in chimeric mosaic mice. In addition, pharmacological PFKFB3 blockade reduces pathological angiogenesis with modest systemic effects, likely because it decreases glycolysis only partially and transiently.
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Sandra
authors: S
authors: Schoors
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Anna Rita
authors: AR
authors: Cantelmo
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Maria
authors: M
authors: Georgiadou
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Peter
authors: P
authors: Stapor
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Xingwu
authors: X
authors: Wang
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Annelies
authors: A
authors: Quaegebeur
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Sandra
authors: S
authors: Cauwenberghs
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Brian W
authors: BW
authors: Wong
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Francesco
authors: F
authors: Bifari
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Ilaria
authors: I
authors: Decimo
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Luc
authors: L
authors: Schoonjans
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Katrien
authors: K
authors: De Bock
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Mieke
authors: M
authors: Dewerchin
authors: Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; University of Leuven; Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link; Vesalius Research Center; Department of Oncology; VIB; Leuven, Belgium.
authors: Peter
authors: P
authors: Carmeliet
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000254:growth & development* / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics*; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics*; D025481:Phosphofructokinase-2 / Q000235:genetics* / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D051880:Receptors, Notch; C107345:PFKFB3 protein, human; D025481:Phosphofructokinase-2
keywords: angiogenesis; endothelial cell; glycolysis; metabolism; vessel sprouting