New anti-nodal monoclonal antibodies targeting the nodal pre-helix loop involved in cripto-1 binding

Annalia Focà, Luca Sanguigno, Giuseppina Focà, Luigi Strizzi, Roberta Iannitti, Rosanna Palumbo, Mary J.C. Hendrix, Antonio Leonardi, Menotti Ruvo, Annamaria Sandomenico*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)21342-21362
Number of pages21
JournalInternational journal of molecular sciences
Volume16
Issue number9
DOIs
StatePublished - Sep 7 2015

Keywords

  • Fab fragments
  • Melanoma
  • Monoclonal antibody
  • Nodal
  • SPR

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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