Cargando…

Effects of a novel Nodal-targeting monoclonal antibody in melanoma

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Strizzi, Luigi, Sandomenico, Annamaria, Margaryan, Naira V., Focà, Annalia, Sanguigno, Luca, Bodenstine, Thomas M., Chandler, Grace S., Reed, David W., Gilgur, Alina, Seftor, Elisabeth A., Seftor, Richard E.B., Khalkhali-Ellis, Zhila, Leonardi, Antonio, Ruvo, Menotti, Hendrix, Mary J.C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741437/
https://www.ncbi.nlm.nih.gov/pubmed/26460952
_version_ 1782413990922551296
author Strizzi, Luigi
Sandomenico, Annamaria
Margaryan, Naira V.
Focà, Annalia
Sanguigno, Luca
Bodenstine, Thomas M.
Chandler, Grace S.
Reed, David W.
Gilgur, Alina
Seftor, Elisabeth A.
Seftor, Richard E.B.
Khalkhali-Ellis, Zhila
Leonardi, Antonio
Ruvo, Menotti
Hendrix, Mary J.C.
author_facet Strizzi, Luigi
Sandomenico, Annamaria
Margaryan, Naira V.
Focà, Annalia
Sanguigno, Luca
Bodenstine, Thomas M.
Chandler, Grace S.
Reed, David W.
Gilgur, Alina
Seftor, Elisabeth A.
Seftor, Richard E.B.
Khalkhali-Ellis, Zhila
Leonardi, Antonio
Ruvo, Menotti
Hendrix, Mary J.C.
author_sort Strizzi, Luigi
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4741437
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-47414372016-03-15 Effects of a novel Nodal-targeting monoclonal antibody in melanoma Strizzi, Luigi Sandomenico, Annamaria Margaryan, Naira V. Focà, Annalia Sanguigno, Luca Bodenstine, Thomas M. Chandler, Grace S. Reed, David W. Gilgur, Alina Seftor, Elisabeth A. Seftor, Richard E.B. Khalkhali-Ellis, Zhila Leonardi, Antonio Ruvo, Menotti Hendrix, Mary J.C. Oncotarget Priority Research Paper 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. Impact Journals LLC 2015-10-09 /pmc/articles/PMC4741437/ /pubmed/26460952 Text en Copyright: © 2015 Strizzi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Priority Research Paper
Strizzi, Luigi
Sandomenico, Annamaria
Margaryan, Naira V.
Focà, Annalia
Sanguigno, Luca
Bodenstine, Thomas M.
Chandler, Grace S.
Reed, David W.
Gilgur, Alina
Seftor, Elisabeth A.
Seftor, Richard E.B.
Khalkhali-Ellis, Zhila
Leonardi, Antonio
Ruvo, Menotti
Hendrix, Mary J.C.
Effects of a novel Nodal-targeting monoclonal antibody in melanoma
title Effects of a novel Nodal-targeting monoclonal antibody in melanoma
title_full Effects of a novel Nodal-targeting monoclonal antibody in melanoma
title_fullStr Effects of a novel Nodal-targeting monoclonal antibody in melanoma
title_full_unstemmed Effects of a novel Nodal-targeting monoclonal antibody in melanoma
title_short Effects of a novel Nodal-targeting monoclonal antibody in melanoma
title_sort effects of a novel nodal-targeting monoclonal antibody in melanoma
topic Priority Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741437/
https://www.ncbi.nlm.nih.gov/pubmed/26460952
work_keys_str_mv AT strizziluigi effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT sandomenicoannamaria effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT margaryannairav effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT focaannalia effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT sanguignoluca effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT bodenstinethomasm effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT chandlergraces effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT reeddavidw effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT gilguralina effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT seftorelisabetha effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT seftorrichardeb effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT khalkhalielliszhila effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT leonardiantonio effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT ruvomenotti effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma
AT hendrixmaryjc effectsofanovelnodaltargetingmonoclonalantibodyinmelanoma