Further Pharmacological and Genetic Evidence for the Efficacy of PlGF Inhibition in Cancer and Eye Disease

被引：247

作者：

Van de Veire, Sara ^{[1
,2
,3
]}

Stalmans, Ingeborg ^{[3
]}

Heindryckx, Femke ^{[4
]}

Oura, Hajimu ^{[5
]}

Tijeras-Raballand, Annemilai ^{[6
]}

Schmidt, Thomas ^{[1
,2
]}

Loges, Sonja ^{[1
,2
]}

Albrecht, Imke ^{[7
]}

Jonckx, Bart ^{[2
]}

Vinckier, Stefan ^{[1
,2
]}

Van Steenkiste, Christophe ^{[4
]}

Tugues, Sonia ^{[8
,9
]}

Rolny, Charlotte ^{[9
]}

De Mol, Maria ^{[1
,2
]}

Dettori, Daniela ^{[1
,2
]}

Hainaud, Patricia ^{[6
]}

Coenegrachts, Lieve ^{[10
]}

Contreres, Jean-Olivier ^{[6
]}

Van Bergen, Tine ^{[3
]}

Cuervo, Henar ^{[1
,2
]}

Xiao, Wei-Hong ^{[11
]}

Le Henaff, Carole ^{[6
]}

Buysschaert, Ian ^{[1
,2
]}

Masouleh, Behzad Kharabi ^{[1
,2
]}

Geerts, Anja ^{[4
]}

Schomber, Tibor ^{[7
]}

Bonnin, Philippe ^{[6
]}

Lambert, Vincent ^{[12
]}

Haustraete, Jurgen ^{[13
]}

Zacchigna, Serena ^{[14
]}

Rakic, Jean-Marie ^{[12
]}

Jimenez, Wladimiro ^{[8
,15
]}

Noel, Agnes ^{[12
]}

Giacca, Mauro ^{[14
]}

Colle, Isabelle ^{[4
]}

Foidart, Jean-Michel ^{[12
]}

Tobelem, Gerard ^{[6
]}

Morales-Ruiz, Manuel ^{[8
]}

Vilar, Jose ^{[16
]}

Maxwell, Patrick ^{[17
]}

Vinores, Stanley A. ^{[1
,2
,11
]}

Carmeliet, Geert ^{[10
]}

Dewerchin, Mieke ^{[1
,2
]}

Claesson-Welsh, Lena ^{[9
]}

Dupuy, Evelyne ^{[6
]}

Van Vlierberghe, Hans ^{[4
]}

Christofori, Gerhard ^{[7
]}

Mazzone, Massimiliano ^{[1
,2
]}

Detmar, Michael ^{[5
]}

Collen, Desire ^{[2
]}

机构：

[1] Katholieke Univ Leuven, Vesalius Res Ctr, B-3000 Louvain, Belgium

[2] VIB, Vesalius Res Ctr, B-3000 Louvain, Belgium

[3] Katholieke Univ Leuven, Lab Ophthalmol, B-3000 Louvain, Belgium

[4] Ghent Univ Hosp, Dept Gastroenterol & Hepatol, B-9000 Ghent, Belgium

[5] ETH, Inst Pharmaceut Sci, CH-8057 Zurich, Switzerland

[6] INSERM, U965, Inst Vaisseaux & Sang Angiogenese & Rech Translat, Paris, France

[7] Univ Basel, Inst Biochem & Genet, CH-4051 Basel, Switzerland

[8] Univ Barcelona, Biochem & Mol Genet Serv, IDIBAPS, Hosp Clin Barcelona,CIBEREHD, E-08036 Barcelona, Spain

[9] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, S-75185 Uppsala, Sweden

[10] Katholieke Univ Leuven, Lab Expt Med & Endocrinol, B-3000 Louvain, Belgium

[11] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA

[12] Univ Liege, Lab Tumour & Dev Biol, GIGA Canc, B-4000 Liege, Belgium

[13] VIB, Prot Serv Facil, B-9052 Ghent, Belgium

[14] Int Ctr Genet Engn & Biotechnol, I-34149 Trieste, Italy

[15] Univ Barcelona, Dept Physiol, Barcelona 08036, Spain

[16] Univ Paris 05, INSERM, U970, Hop Europeen Georges Pompidou,Cardiovasc Res Ctr, F-75270 Paris 06, France

[17] UCL, Rayne Inst, Div Med, London WC1E 6JF, England

来源：

CELL | 2010年 / 141卷 / 01期

关键词：

PLACENTA GROWTH-FACTOR; HEPATOCELLULAR-CARCINOMA; PATHOLOGICAL CONDITIONS; MOUSE MODEL; METASTASIS; ANGIOGENESIS; MICE; PROGRESSION; HYPOXIA; LUNG;

D O I：

10.1016/j.cell.2010.02.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：178 / 190

页数：13

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