Angiostatin anti-angiogenesis requires IL-12: the innate immune system as a key target.

Journal of Translational Medicine
Adriana AlbiniDouglas M Noonan

Abstract

Angiostatin, an endogenous angiogenesis inhibitor, is a fragment of plasminogen. Its anti-angiogenic activity was discovered with functional assays in vivo, however, its direct action on endothelial cells is moderate and identification of definitive mechanisms of action has been elusive to date. We had previously demonstrated that innate immune cells are key targets of angiostatin, however the pathway involved in this immune-related angiogenesis inhibition was not known. Here we present evidence that IL-12, a principal TH1 cytokine with potent anti-angiogenic activity, is the mediator of angiostatin's activity. Function blocking antibodies and gene-targeted animals were employed or in vivo studies using the subcutaneous matrigel model of angiogenesis. Quantitative real-time PCR were used to assess modulation of cytokine production in vitro. Angiostatin inhibts angiogenesis induced by VEGF-TNFalpha or supernatants of Kaposi's Sarcoma cells (a highly angiogenic and inflammation-associated tumor). We found that function-blocking antibodies to IL-12 reverted angiostatin induced angiogenesis inhibition. The use of KO animal models revealed that angiostatin is unable to exert angiogenesis inhibition in mice with gene-targeted deletio...Continue Reading

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Citations

Apr 13, 2010·Clinical & Experimental Metastasis·Adriana AlbiniUlrich Pfeffer
Jul 27, 2011·Journal of Mammary Gland Biology and Neoplasia·Tim Kees, Mikala Egeblad
May 26, 2012·British Journal of Pharmacology·M SolinasD Parolaro
Jan 29, 2014·International Journal of Rheumatic Diseases·Gholamreza AziziAbbas Mirshafiey
Nov 18, 2014·Biochemical Society Transactions·Arjan W GriffioenPatrycja Nowak-Sliwinska
Nov 24, 2011·Ocular Immunology and Inflammation·Hassan GhasemiZuhair Mohammad Hassan
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Jul 30, 2014·Frontiers in Oncology·Antonino BrunoLorenzo Mortara
Aug 9, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Joan J CastellanoMariano Monzo
Dec 7, 2016·Modern Rheumatology·Jatin SharmaC Subathra Devi
Oct 17, 2018·Future Oncology·Premal H ThakerKhursheed Anwer
Sep 1, 2009·Expert Review of Clinical Pharmacology·Anupama Sharma, Brian J Czerniecki

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Methods Mentioned

BETA
ELISA
FCS
FACS
PCR

Software Mentioned

Prism ( Graph Pad )
Qgene

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