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Int. J. Mol. Sci. 2015, 16(9), 21342-21362; doi:10.3390/ijms160921342

New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding

1
Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR) and Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), Università degli Studi di Napoli "Federico II", Naples 80134, Italy
2
Department of Pharmacy, Università degli Studi di Napoli "Federico II", Naples 80131, Italy
3
Bioker Multimedica, Naples 80131, Italy
4
Program in Cancer Biology and Epigenomics, Stanley Manne Children's Research Institute at Ann and Robert H. Lurie Children's Hospital of Chicago, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
5
Department of Molecular Medicine and Medical Biotechnologies, Università degli Studi di Napoli "Federico II", Naples 80131, Italy
*
Authors to whom correspondence should be addressed.
Academic Editor: Andrzej Slominski
Received: 28 July 2015 / Revised: 21 August 2015 / Accepted: 27 August 2015 / Published: 7 September 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [1399 KB, uploaded 7 September 2015]   |  

Abstract

Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to block the Cripto-1-mediated signalling. To achieve this, antibodies were raised against hNodal(44–67) and mAbs generated by the hybridoma technology. We have selected one mAb, named 3D1, which strongly associates with full-length rhNodal (KD 1.4 nM) and recognizes the endogenous protein in a panel of human melanoma cell lines by western blot and FACS analyses. 3D1 inhibits the Nodal-Cripto-1 binding and blocks Smad2/3 phosphorylation. Data suggest that inhibition of the Nodal-Cripto-1 axis is a valid therapeutic approach against melanoma and 3D1 is a promising and interesting agent for blocking Nodal-Cripto mediated tumor development. These findings increase the interest for Nodal as both a diagnostic and prognostic marker and as a potential new target for therapeutic intervention. View Full-Text
Keywords: Fab fragments; monoclonal antibody; melanoma; nodal; SPR Fab fragments; monoclonal antibody; melanoma; nodal; SPR
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Focà, A.; Sanguigno, L.; Focà, G.; Strizzi, L.; Iannitti, R.; Palumbo, R.; Hendrix, M.J.C.; Leonardi, A.; Ruvo, M.; Sandomenico, A. New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding. Int. J. Mol. Sci. 2015, 16, 21342-21362.

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