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Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4 monoclonal antibody
Hernández, José Luis; Padilla, Laura; Dakhel, Sheila; Coll, Toni; Hervas, Rosa; Adan, Jaume; Masa, Marc; Mitjans, Francesc; Martinez, Josep Maria; Coma i Bassas, Sílvia; Rodríguez Gallego, Laura; Noé Mata, Verónica; Ciudad i Gómez, Carlos Julián; Blasco, Francesc; Messeguer i Peypoch, Ramon
Universitat de Barcelona
S100A4, a member of the S100 calcium-binding protein family secreted by tumor and stromal cells, supports tumorigenesis by stimulating angiogenesis. We demonstrated that S100A4 synergizes with vascular endothelial growth factor (VEGF), via the RAGE receptor, in promoting endothelial cell migration by increasing KDR expression and MMP-9 activity. In vivo overexpression of S100A4 led to a significant increase in tumor growth and vascularization in a human melanoma xenograft M21 model. Conversely, when silencing S100A4 by shRNA technology, a dramatic decrease in tumor development of the pancreatic MiaPACA-2 cell line was observed. Based on these results we developed 5C3, a neutralizing monoclonal antibody against S100A4. This antibody abolished endothelial cell migration, tumor growth and angiogenesis in immunodeficient mouse xenograft models of MiaPACA-2 and M21-S100A4 cells. It is concluded that extracellular S100A4 inhibition is an attractive approach for the treatment of human cancer.
13-02-2014
Càncer
Proteïnes de la sang
Angiogènesi
Anticossos monoclonals
Cancer
Blood proteins
Neovascularization
Monoclonal antibodies
cc-by (c) Hernández, José Luis et al., 2013
http://creativecommons.org/licenses/by/3.0/es
Artículo
info:eu-repo/semantics/publishedVersion
Public Library of Science (PLoS)
         

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