Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease.

Abstract

Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models as well as ocular neovascularization to report further evidence in support of our original findings of PlGF as a promising target for anticancer therapies. We present evidence for the efficacy of additional anti-PlGF antibodies and their ability to phenocopy genetic deficiency or silencing of PlGF in cancer and ocular disease but also show that not all anti-PlGF antibodies are effective. We also provide additional evidence for the specificity of our anti-PlGF antibody and experiments to suggest that anti-PlGF treatment will not be effective for all tumors and why. Further, we show that PlGF blockage inhibits vessel abnormalization rather than density in certain tumors while enhancing VEGF-targeted inhibition in ocular disease. Our findings warrant further testing of anti-PlGF therapies.

• Authors: Sara Van de Veire, Ingeborg Stalmans, Femke Heindryckx, Hajimu Oura, Annemilaï Tijeras-Raballand, Thomas Schmidt, Sonja Loges, Imke Albrecht, Bart Jonckx, Stefan Vinckier, Christophe Van Steenkiste, Sònia Tugues, Charlotte Rolny, Maria De Mol, Daniela Dettori, Patricia Hainaud, Lieve Coenegrachts, Jean-Olivier Contreres, Tine Van Bergen, Henar Cuervo, Wei-Hong Xiao, Carole Le Henaff, Ian Buysschaert, Behzad Kharabi Masouleh, Anja Geerts, Tibor Schomber, Philippe Bonnin, Vincent Lambert, Jurgen Haustraete, Serena Zacchigna, Jean-Marie Rakic, Wladimiro Jiménez, Agnes Noël, Mauro Giacca, Isabelle Colle, Jean-Michel Foidart, Gerard Tobelem, Manuel Morales-Ruiz, José Vilar, Patrick Maxwell, Stanley A Vinores, Geert Carmeliet, Mieke Dewerchin, Lena Claesson-Welsh, Evelyne Dupuy, Hans Van Vlierberghe, Gerhard Christofori, Massimiliano Mazzone, Michael Detmar, Désiré Collen, Peter Carmeliet
• Journal: Cell (Cell) Vol. 141 Issue 1 Pg. 178-90 (Apr 02 2010) ISSN: 1097-4172 [Electronic] United States
• PMID: 20371353 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal
• PGF protein, human
• Pgf protein, mouse
• Pregnancy Proteins
• Placenta Growth Factor

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Antibodies, Monoclonal (therapeutic use)
• Carcinoma, Hepatocellular (blood supply, prevention & control)
• Choroid (blood supply)
• Disease Models, Animal
• Eye Diseases (pathology)
• Humans
• Liver Neoplasms, Experimental (blood supply, prevention & control)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Transgenic
• Neovascularization, Physiologic (drug effects)
• Papilloma (blood supply, chemically induced, prevention & control)
• Placenta Growth Factor
• Pregnancy Proteins (antagonists & inhibitors, metabolism)
• Skin Neoplasms (blood supply, chemically induced, prevention & control)