HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PIGF

被引：575

作者：

Rolny, Charlotte ^{[1
,2
,3
]}

Mazzone, Massimiliano ^{[2
,3
]}

Tugues, Sonia ^{[1
]}

Laoui, Damya ^{[4
,5
]}

Johansson, Irja ^{[1
]}

Coulon, Cathy ^{[2
,3
]}

Squadrito, Mario Leonardo ^{[6
,10
]}

Segura, Inmaculada ^{[2
,3
]}

Li, Xiujuan ^{[1
]}

Knevels, Ellen ^{[2
,3
]}

Costa, Sandra ^{[2
,3
]}

Vinckier, Stefan ^{[2
,3
]}

Dresselaer, Tom ^{[7
]}

Akerud, Peter ^{[8
]}

De Mol, Maria ^{[2
,3
]}

Salomaki, Henriikka ^{[1
]}

Phillipson, Mia ^{[9
]}

Wyns, Sabine ^{[2
,3
]}

Larsson, Erik ^{[1
]}

Buysschaert, Ian ^{[2
,3
]}

Botling, Johan ^{[1
]}

Himmelreich, Uwe ^{[7
]}

Van Ginderachter, Jo A. ^{[4
,5
]}

De Palma, Michele ^{[6
,10
]}

Dewerchin, Mieke ^{[2
,3
]}

Claesson-Welsh, Lena ^{[1
]}

Carmeliet, Peter ^{[2
,3
]}

机构：

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

[2] VIB, Vesalius Res Ctr, Louvain, Belgium

[3] Katholieke Univ Leuven, Vesalius Res Ctr, Louvain, Belgium

[4] VIB, Dept Mol Cellular Interact, Lab Cellular Mol Immunol, Brussels, Belgium

[5] Vrije Univ Brussel, Lab Cellular Mol Immunol, Brussels, Belgium

[6] HSR TIGET, Angiogenesis & Tumor Targeting Unit, I-20132 Milan, Italy

[7] Katholieke Univ Leuven, MoSAIC, Louvain, Belgium

[8] Uppsala Univ, Dept Surg Sci, Univ Hosp, S-75185 Uppsala, Sweden

[9] Uppsala Univ, Dept Med Cell Biol, Biomed Ctr, S-75185 Uppsala, Sweden

[10] Univ Vita Salute San Raffaele, San Raffaele Sci Inst, I-20132 Milan, Italy

来源：

CANCER CELL | 2011年 / 19卷 / 01期

基金：

欧洲研究理事会; 瑞典研究理事会;

关键词：

HISTIDINE-RICH GLYCOPROTEIN; ANTI-ANGIOGENIC THERAPY; TIE2-EXPRESSING MONOCYTES; COAGULATION SYSTEMS; PLASMA; FRAGMENT; EFFICACY; IMMUNE; DOMAIN; BINDS;

D O I：

10.1016/j.ccr.2010.11.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Polarization of tumor-associated macrophages (TAMs) to a proangiogenic/immune-suppressive (M2-like) phenotype and abnormal, hypoperfused vessels are hallmarks of malignancy, but their molecular basis and interrelationship remains enigmatic. We report that the host-produced histidine-rich glycoprotein (HRG) inhibits tumor growth and metastasis, while improving chemotherapy. By skewing TAM polarization away from the M2- to a tumor-inhibiting M1-like phenotype, HRG promotes antitumor immune responses and vessel normalization, effects known to decrease tumor growth and metastasis and to enhance chemotherapy. Skewing of TAM polarization by HAG relies substantially on downregulation of placental growth factor (PIGF). Besides unveiling an important role for TAM polarization in tumor vessel abnormalization, and its regulation by HRG/PIGF, these findings offer therapeutic opportunities for anticancer and antiangiogenic treatment.

引用

页码：31 / 44

页数：14

共 34 条

[11] FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy? [J].

Fischer, Christian ;

Mazzone, Massimiliano ;

Jonckx, Bart ;

Carmeliet, Peter .

NATURE REVIEWS CANCER, 2008, 8 (12) :942-956

[12] Histidine-Proline Rich Glycoprotein (HPRG) binds and transiduces anti-angiogenic signals through cell surface tropomyosin on endothelial cells [J].

Guan, XJ ;

Juarez, JC ;

Qi, XP ;

Shipulina, NV ;

Shaw, DE ;

Morgan, WT ;

McCrae, KR ;

Mazar, AR ;

Doñate, F .

THROMBOSIS AND HAEMOSTASIS, 2004, 92 (02) :403-412

[13] Re-educating tumor-associated macrophages by targeting NF-κB [J].

Hagemann, Thorsten ;

Lawrence, Toby ;

McNeish, Iain ;

Charles, Kellie A. ;

Kulbe, Hagen ;

Thompson, Richard G. ;

Robinson, Stephen C. ;

Balkwill, Frances R. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (06) :1261-1268

[14] Vascular normalization in Rgs5-deficient tumours promotes immune destruction [J].

Hamzah, Juliana ;

Jugold, Manfred ;

Kiessling, Fabian ;

Rigby, Paul ;

Manzur, Mitali ;

Marti, Hugo H. ;

Rabie, Tamer ;

Kaden, Sylvia ;

Groene, Hermann-Josef ;

Haemmerling, Guenter J. ;

Arnold, Bernd ;

Ganss, Ruth .

NATURE, 2008, 453 (7193) :410-U67

[15] Malignant cell-derived PlGF promotes normalization and remodeling of the tumor vasculature [J].

Hedlund, Eva-Maria ;

Hosaka, Kayoko ;

Zhong, Zhaodong ;

Cao, Renhai ;

Cao, Yihai .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (41) :17505-17510

[16] Murine histidine-rich glycoprotein: Cloning, characterization and cellular origin [J].

Hulett, MD ;

Parish, CR .

IMMUNOLOGY AND CELL BIOLOGY, 2000, 78 (03) :280-287

[17] Histidine-rich glycoprotein: A novel adaptor protein in plasma that modulates the immune, vascular and coagulation systems [J].

Jones, AL ;

Hulett, MD ;

Parish, CR .

IMMUNOLOGY AND CELL BIOLOGY, 2005, 83 (02) :106-118

[18] Histidine-rich glycoprotein binds to cell-surface heparan sulfate via its N-terminal domain following Zn2+ chelation [J].

Jones, AL ;

Hulett, MD ;

Parish, CR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (29) :30114-30122

[19] Influence of applied volume on efficacy of 3-minute surgical reference disinfection method prEN 12791 [J].

Kampf, G ;

Ostermeyer, C .

APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2004, 70 (12) :7066-7069

[20] Histidine-Rich Glycoprotein Can Prevent Development of Mouse Experimental Glioblastoma [J].

Karrlander, Maria ;

Lindberg, Nanna ;

Olofsson, Tommie ;

Kastemar, Marianne ;

Olsson, Anna-Karin ;

Uhrbom, Lene .

PLOS ONE, 2009, 4 (12)

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