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Effects of a novel Nodal-targeting monoclonal antibody in melanoma

Luigi Strizzi, Annamaria Sandomenico, Naira V. Margaryan, Annalia Focà, Luca Sanguigno, Thomas M. Bodenstine, Grace S. Chandler, David W. Reed, Alina Gilgur, Elisabeth A. Seftor, Richard E.B. Seftor, Zhila Khalkhali-Ellis, Antonio Leonardi, Menotti Ruvo and Mary J.C. Hendrix _

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Oncotarget. 2015; 6:34071-34086. https://doi.org/10.18632/oncotarget.6049

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Luigi Strizzi1,2,*, Annamaria Sandomenico5,*, Naira V. Margaryan1, Annalia Focà5, Luca Sanguigno6, Thomas M. Bodenstine1, Grace S. Chandler1, David W. Reed1, Alina Gilgur1, Elisabeth A. Seftor1, Richard E.B. Seftor1,3, Zhila Khalkhali-Ellis1,3,4, Antonio Leonardi6, Menotti Ruvo5 and Mary J.C. Hendrix1,4

1 Cancer Biology and Epigenomics Program, Stanley Manne Children’s Research Institute, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

2 Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

3 Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

4 Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

5 Istituto di Biostrutture e Bioimmagini del CNR and CIRPeB, Università Federico II di Napoli, Naples, Italy

6 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II di Napoli, Naples, Italy

* These authors have contributed equally to this work

Correspondence to:

Mary J.C. Hendrix, email:

Menotti Ruvo, email:

Antonio Leonardi, email:

Keywords: Nodal, cancer, antibody, ELISA, therapy

Received: July 28, 2015 Accepted: September 24, 2015 Published: October 09, 2015


Nodal is highly expressed in various human malignancies, thus supporting the rationale for exploring Nodal as a therapeutic target. Here, we describe the effects of a novel monoclonal antibody (mAb), 3D1, raised against human Nodal. In vitro treatment of C8161 human melanoma cells with 3D1 mAb shows reductions in anchorage-independent growth and vasculogenic network formation. 3D1 treated cells also show decreases of Nodal and downstream signaling molecules, P-Smad2 and P-ERK and of P-H3 and CyclinB1, with an increase in p27. Similar effects were previously reported in human breast cancer cells where Nodal expression was generally down-regulated; following 3D1 mAb treatment, both Nodal and P-H3 levels are reduced. Noteworthy is the reduced growth of human melanoma xenografts in Nude mice treated with 3D1 mAb, where immunostaining of representative tumor sections show diminished P-Smad2 expression. Similar effects both in vitro and in vivo were observed in 3D1 treated A375SM melanoma cells harboring the active BRAF(V600E) mutation compared to treatments with IgG control or a BRAF inhibitor, dabrafenib. Finally, we describe a 3D1-based ELISA for the detection of Nodal in serum samples from cancer patients. These data suggest the potential of 3D1 mAb for selecting and targeting Nodal expressing cancers.

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