New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding
AbstractNodal 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
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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.
Focà A, Sanguigno L, Focà G, Strizzi L, Iannitti R, Palumbo R, Hendrix MJC, Leonardi A, Ruvo M, Sandomenico A. New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding. International Journal of Molecular Sciences. 2015; 16(9):21342-21362.Chicago/Turabian Style
Focà, Annalia; Sanguigno, Luca; Focà, Giuseppina; Strizzi, Luigi; Iannitti, Roberta; Palumbo, Rosanna; Hendrix, Mary J.C.; Leonardi, Antonio; Ruvo, Menotti; Sandomenico, Annamaria. 2015. "New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding." Int. J. Mol. Sci. 16, no. 9: 21342-21362.