Title: Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels
Authors: Fischer, Christian
Jonckx, Bart
Mazzone, Max
Zacchigna, Serena
Loges, Sonja
Pattarini, Lucia
Chorianopoulos, Emmanuel
Liesenborghs, Laurens
Koch, Marta
De Mol, Maria
Autiero, Monica
Wyns, Sabine
Plaisance, Stephane
Moons, Lieve
van Rooijen, Nico
Giacca, Mauro
Stassen, Jean-Marie
Dewerchin, Mieke
Collen, Desire
Carmeliet, Peter # ×
Issue Date: Nov-2007
Publisher: MIT Press
Series Title: Cell vol:131 issue:3 pages:463-475
Abstract: Novel antiangiogenic strategies with complementary mechanisms are needed to maximize efficacy and minimize resistance to current angiogenesis inhibitors. We explored the therapeutic potential and mechanisms of alphaPlGF, an antibody against placental growth factor (PlGF), a VEGF homolog, which regulates the angiogenic switch in disease, but not in health. alphaPlGF inhibited growth and metastasis of various tumors, including those resistant to VEGF(R) inhibitors (VEGF(R)Is), and enhanced the efficacy of chemotherapy and VEGF(R)Is. alphaPlGF inhibited angiogenesis, lymphangiogenesis, and tumor cell motility. Distinct from VEGF(R)Is, alphaPlGF prevented infiltration of angiogenic macrophages and severe tumor hypoxia, and thus, did not switch on the angiogenic rescue program responsible for resistance to VEGF(R)Is. Moreover, it did not cause or enhance VEGF(R)I-related side effects. The efficacy and safety of alphaPlGF, its pleiotropic and complementary mechanism to VEGF(R)Is, and the negligible induction of an angiogenic rescue program suggest that alphaPlGF may constitute a novel approach for cancer treatment.
ISSN: 0092-8674
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Animal Physiology and Neurobiology Section - miscellaneous
Vesalius Research Centre (-)
Molecular Genetics Section (-)
Molecular and Vascular Biology
Laboratory of Neurogenetics (-)
Laboratory of Tumor Inflammation and Angiogenesis (VIB-KU Leuven Centre for Cancer Biology) (+)
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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