Priority Research Papers:
Effects of a novel Nodal-targeting monoclonal antibody in melanoma
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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
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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