Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/49886
Title: Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4 monoclonal antibody
Author: 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
Keywords: Càncer
Proteïnes de la sang
Angiogènesi
Anticossos monoclonals
Cancer
Blood proteins
Neovascularization
Monoclonal antibodies
Issue Date: 4-Sep-2013
Publisher: Public Library of Science (PLoS)
Abstract: 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.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0072480
It is part of: PLoS One, 2013, vol. 8, num. 9, p. e72480
Related resource: http://dx.doi.org/10.1371/journal.pone.0072480
URI: http://hdl.handle.net/2445/49886
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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