PlGF Blockade Does Not Inhibit Angiogenesis during Primary Tumor Growth

被引：129

作者：

Bais, Carlos ^{[1
]}

Wu, Xiumin ^{[1
]}

Yao, Jenny ^{[1
]}

Yang, Suya ^{[1
]}

Crawford, Yongping ^{[1
]}

McCutcheon, Krista ^{[1
]}

Tan, Christine ^{[1
]}

Kolumam, Ganesh ^{[1
]}

Vernes, Jean-Michel ^{[1
]}

Eastham-Anderson, Jeffrey ^{[1
]}

Haughney, Peter ^{[1
]}

Kowanetz, Marcin ^{[1
]}

Hagenbeek, Thijs ^{[1
]}

Kasman, Ian ^{[1
]}

Reslan, Hani Bou ^{[1
]}

Ross, Jed ^{[1
]}

Van Bruggen, Nick ^{[1
]}

Carano, Richard A. D. ^{[1
]}

Meng, Yu-Ju Gloria ^{[1
]}

Hongo, Jo-Anne ^{[1
]}

Stephan, Jean-Philippe ^{[1
]}

Shibuya, Masabumi ^{[1
,2
]}

Ferrara, Napoleone ^{[1
]}

机构：

[1] Genentech Inc, San Francisco, CA 94080 USA

[2] Tokyo Med & Dent Univ, Grad Sch Med & Dent, Dept Mol Oncol, Tokyo 1138510, Japan

来源：

CELL | 2010年 / 141卷 / 01期

关键词：

VEGFR1-ACTIVITY-INDEPENDENT METASTASIS FORMATION; HIGH-AFFINITY BINDING; FACTOR RECEPTOR-1; TYROSINE KINASE; IN-VIVO; VEGF; FLT-1; ANTIBODY; TARGETS; CANCER;

D O I：

10.1016/j.cell.2010.01.033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

It has been recently reported that treatment with an anti-placenta growth factor (PlGF) antibody inhibits metastasis and primary tumor growth. Here we show that, although anti-PlGF treatment inhibited wound healing, extravasation of B16F10 cells, and growth of a tumor engineered to overexpress the PlGF receptor (VEGFR-1), neutralization of PlGF using four novel blocking antibodies had no significant effect on tumor angiogenesis in 15 models. Also, genetic ablation of the tyrosine kinase domain of VEGFR-1 in the host did not result in growth inhibition of the anti-VEGF-A sensitive or resistant tumors tested. Furthermore, combination of anti-PlGF with anti-VEGF-A antibodies did not result in greater antitumor efficacy than anti-VEGF-A monotherapy. In conclusion, our data argue against an important role of PlGF during primary tumor growth in most models and suggest that clinical evaluation of anti-PlGF antibodies may be challenging.

引用

页码：166 / 177

页数：12

共 49 条

[1]

[Anonymous], NAT MED

[2] Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders [J].

Autiero, M ;

Luttun, A ;

Tjwa, M ;

Carmeliet, P .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2003, 1 (07) :1356-1370

[3] Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis [J].

Avecilla, ST ;

Hattori, K ;

Heissig, B ;

Tejada, R ;

Liao, F ;

Shido, K ;

Jin, DK ;

Dias, S ;

Zhang, F ;

Hartman, TE ;

Hackett, NR ;

Crystal, RG ;

Witte, L ;

Hicklin, DJ ;

Bohlen, P ;

Eaton, D ;

Lyden, D ;

de Sauvage, F ;

Rafii, S .

NATURE MEDICINE, 2004, 10 (01) :64-71

[4] Heterodimers of placenta growth factor vascular endothelial growth factor - Endothelial activity, tumor cell expression, and high affinity binding to Flk-1/KDR [J].

Cao, YH ;

Chen, H ;

Zhou, L ;

Chiang, MK ;

AnandApte, B ;

Weatherbee, JA ;

Wang, YD ;

Fang, FY ;

Flanagan, JG ;

Tsang, MLS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (06) :3154-3162

[5] Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions [J].

Carmeliet, P ;

Moons, L ;

Luttun, A ;

Vincenti, V ;

Compernolle, V ;

De Mol, M ;

Wu, Y ;

Bon, F ;

Devy, L ;

Beck, H ;

Scholz, D ;

Acker, T ;

DiPalma, T ;

Dewerchin, M ;

Noel, A ;

Stalmans, I ;

Barra, A ;

Blacher, S ;

Vandendriessche, T ;

Ponten, A ;

Eriksson, U ;

Plate, KH ;

Foidart, JM ;

Schaper, W ;

Charnock-Jones, DS ;

Hicklin, DJ ;

Herbert, JM ;

Collen, D ;

Persico, MG .

NATURE MEDICINE, 2001, 7 (05) :575-583

[6] Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele [J].

Carmeliet, P ;

Ferreira, V ;

Breier, G ;

Pollefeyt, S ;

Kieckens, L ;

Gertsenstein, M ;

Fahrig, M ;

Vandenhoeck, A ;

Harpal, K ;

Eberhardt, C ;

Declercq, C ;

Pawling, J ;

Moons, L ;

Collen, D ;

Risau, W ;

Nagy, A .

NATURE, 1996, 380 (6573) :435-439

[7] Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors [J].

Casanovas, O ;

Hicklin, DJ ;

Bergers, G ;

Hanahan, D .

CANCER CELL, 2005, 8 (04) :299-309

[8] Placenta growth factor in diabetic wound healing - Altered expression and therapeutic potential [J].

Cianfarani, Francesca ;

Zambruno, Giovanna ;

Brogelli, Laura ;

Sera, Francesco ;

Lacal, Pedro Miguel ;

Pesce, Maurizio ;

Capogrossi, Maurizio C. ;

Failla, Cristina Maria ;

Napolitano, Monica ;

Odorisio, Teresa .

AMERICAN JOURNAL OF PATHOLOGY, 2006, 169 (04) :1167-1182

[9] Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets [J].

Clynes, RA ;

Towers, TL ;

Presta, LG ;

Ravetch, JV .

NATURE MEDICINE, 2000, 6 (04) :443-446

[10] The second immunoglobulin-like domain of the VEGF tyrosine kinase receptor Flt-1 determines ligand binding and may initiate a signal transduction cascade [J].

DavisSmyth, T ;

Chen, H ;

Park, J ;

Presta, LG ;

Ferrara, N .

EMBO JOURNAL, 1996, 15 (18) :4919-4927

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