title: Delivery of soluble VEGF receptor 1 (sFlt1) by gene electrotransfer as a new antiangiogenic cancer therapy.
abstract: Since tumor growth is highly dependent on the formation of new blood vessels, angiogenesis inhibitors have become important players in anticancer treatments. Although less cytotoxic than conventional chemotherapy, most of the available antiangiogenic agents may provoke severe adverse effects which can limit their use. The design of new antiangiogenic strategies therefore requires integrating an early evaluation of possible interference with quiescent endothelial cells and nontumor angiogenesis. Here, we describe such a novel antiangiogenic approach based on the in vivo delivery by gene electrotransfer of a negative regulator of angiogenesis, namely, sFlt1. We found that this soluble variant of the vascular endothelial growth factor receptor 1 (Flt1, also known as VEGFR1), which acts as a VEGF trap, differentially influences tumor and postischemic hind limb angiogenesis in mice. sFlt1 gene electrotransfer in tibial cranial muscle leads to high sFlt1 protein expression and secretion, leading to a significant delay in the growth of syngeneic tumors but not altering the revascularization of ischemic peripheral tissue. The higher sensitivity of tumor-bearing animals toward sFlt1 trapping effects (vs ischemia-recovering animals) might be explained by a distinct pattern of VEGF release, as shown by VEGF measurements in plasma and tissue. In conclusion, our data support sFlt1 gene electrotransfer as a novel and safe modality to target VEGF-driven tumor angiogenesis and to maintain unaltered the recovery potential of ischemic tissues.
authors.affiliation: Angiogenesis and Cancer Research Laboratory, Pole of Pharmacology and Therapeutics, Institute of Experimental and Clinical Research, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Julien
authors.initials: J
authors.lastname: Verrax
authors.forename: Florence
authors.initials: F
authors.lastname: Defresne
authors.forename: Florence
authors.initials: F
authors.lastname: Lair
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Vandermeulen
authors.forename: Géraldine
authors.initials: G
authors.lastname: Rath
authors.forename: Chantal
authors.initials: C
authors.lastname: Dessy
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000628:therapy; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000628:therapy; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
chemical_list: D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1