Research Article
Therapeutic Targeting of Tumor Growth and Angiogenesis with a Novel Anti-S100A4 Monoclonal Antibody
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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.Citation: Hernández JL, Padilla L, Dakhel S, Coll T, Hervas R, et al. (2013) Therapeutic Targeting of Tumor Growth and Angiogenesis with a Novel Anti-S100A4 Monoclonal Antibody. PLoS ONE 8(9): e72480. doi:10.1371/journal.pone.0072480
Editor: Sujit Basu, Ohio State University, United States of America
Received: March 7, 2013; Accepted: July 10, 2013; Published: September 4, 2013
Copyright: © 2013 Hernández et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The work was supported by Grants from ACC1Ó, the Catalan Business Competitiveness Support Agency and SAF08-043/SAF2011-23582 from “Plan Nacional de Investigación Científica” (Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: J.L. Hernández, L. Padilla, S. Dakhel, T. Coll, R. Hervas, J. Adan, M. Masa, F. Mitjans, J.M. Martinez, R. Messeguer are holders of patent WO/2011/157724: “S100A4 antibodies and therapeutic uses thereof”. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
Editor: Sujit Basu, Ohio State University, United States of America
Received: March 7, 2013; Accepted: July 10, 2013; Published: September 4, 2013
Copyright: © 2013 Hernández et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The work was supported by Grants from ACC1Ó, the Catalan Business Competitiveness Support Agency and SAF08-043/SAF2011-23582 from “Plan Nacional de Investigación Científica” (Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: J.L. Hernández, L. Padilla, S. Dakhel, T. Coll, R. Hervas, J. Adan, M. Masa, F. Mitjans, J.M. Martinez, R. Messeguer are holders of patent WO/2011/157724: “S100A4 antibodies and therapeutic uses thereof”. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
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