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Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms

Podoplanin (PDPN) is a unique transmembrane receptor that promotes tumor cell motility. Indeed, PDPN may serve as a chemotherapeutic target for primary and metastatic cancer cells, particularly oral squamous cell carcinoma (OSCC) cells that cause most oral cancers. Here, we studied how a monoclonal...

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Autores principales: Ochoa-Alvarez, Jhon A., Krishnan, Harini, Pastorino, John G., Nevel, Evan, Kephart, David, Lee, Joseph J., Retzbach, Edward P., Shen, Yongquan, Fatahzadeh, Mahnaz, Baredes, Soly, Kalyoussef, Evelyne, Honma, Masaru, Adelson, Martin E., Kaneko, Mika K., Kato, Yukinari, Young, Mary Ann, Deluca-Rapone, Lisa, Shienbaum, Alan J., Yin, Kingsley, Jensen, Lasse D., Goldberg, Gary S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496201/
https://www.ncbi.nlm.nih.gov/pubmed/25826087
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author Ochoa-Alvarez, Jhon A.
Krishnan, Harini
Pastorino, John G.
Nevel, Evan
Kephart, David
Lee, Joseph J.
Retzbach, Edward P.
Shen, Yongquan
Fatahzadeh, Mahnaz
Baredes, Soly
Kalyoussef, Evelyne
Honma, Masaru
Adelson, Martin E.
Kaneko, Mika K.
Kato, Yukinari
Young, Mary Ann
Deluca-Rapone, Lisa
Shienbaum, Alan J.
Yin, Kingsley
Jensen, Lasse D.
Goldberg, Gary S.
author_facet Ochoa-Alvarez, Jhon A.
Krishnan, Harini
Pastorino, John G.
Nevel, Evan
Kephart, David
Lee, Joseph J.
Retzbach, Edward P.
Shen, Yongquan
Fatahzadeh, Mahnaz
Baredes, Soly
Kalyoussef, Evelyne
Honma, Masaru
Adelson, Martin E.
Kaneko, Mika K.
Kato, Yukinari
Young, Mary Ann
Deluca-Rapone, Lisa
Shienbaum, Alan J.
Yin, Kingsley
Jensen, Lasse D.
Goldberg, Gary S.
author_sort Ochoa-Alvarez, Jhon A.
collection PubMed
description Podoplanin (PDPN) is a unique transmembrane receptor that promotes tumor cell motility. Indeed, PDPN may serve as a chemotherapeutic target for primary and metastatic cancer cells, particularly oral squamous cell carcinoma (OSCC) cells that cause most oral cancers. Here, we studied how a monoclonal antibody (NZ-1) and lectin (MASL) that target PDPN affect human OSCC cell motility and viability. Both reagents inhibited the migration of PDPN expressing OSCC cells at nanomolar concentrations before inhibiting cell viability at micromolar concentrations. In addition, both reagents induced mitochondrial membrane permeability transition to kill OSCC cells that express PDPN by caspase independent nonapoptotic necrosis. Furthermore, MASL displayed a surprisingly robust ability to target PDPN on OSCC cells within minutes of exposure, and significantly inhibited human OSCC dissemination in zebrafish embryos. Moreover, we report that human OSCC cells formed tumors that expressed PDPN in mice, and induced PDPN expression in infiltrating host murine cancer associated fibroblasts. Taken together, these data suggest that antibodies and lectins may be utilized to combat OSCC and other cancers that express PDPN.
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spelling pubmed-44962012015-07-10 Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms Ochoa-Alvarez, Jhon A. Krishnan, Harini Pastorino, John G. Nevel, Evan Kephart, David Lee, Joseph J. Retzbach, Edward P. Shen, Yongquan Fatahzadeh, Mahnaz Baredes, Soly Kalyoussef, Evelyne Honma, Masaru Adelson, Martin E. Kaneko, Mika K. Kato, Yukinari Young, Mary Ann Deluca-Rapone, Lisa Shienbaum, Alan J. Yin, Kingsley Jensen, Lasse D. Goldberg, Gary S. Oncotarget Research Paper Podoplanin (PDPN) is a unique transmembrane receptor that promotes tumor cell motility. Indeed, PDPN may serve as a chemotherapeutic target for primary and metastatic cancer cells, particularly oral squamous cell carcinoma (OSCC) cells that cause most oral cancers. Here, we studied how a monoclonal antibody (NZ-1) and lectin (MASL) that target PDPN affect human OSCC cell motility and viability. Both reagents inhibited the migration of PDPN expressing OSCC cells at nanomolar concentrations before inhibiting cell viability at micromolar concentrations. In addition, both reagents induced mitochondrial membrane permeability transition to kill OSCC cells that express PDPN by caspase independent nonapoptotic necrosis. Furthermore, MASL displayed a surprisingly robust ability to target PDPN on OSCC cells within minutes of exposure, and significantly inhibited human OSCC dissemination in zebrafish embryos. Moreover, we report that human OSCC cells formed tumors that expressed PDPN in mice, and induced PDPN expression in infiltrating host murine cancer associated fibroblasts. Taken together, these data suggest that antibodies and lectins may be utilized to combat OSCC and other cancers that express PDPN. Impact Journals LLC 2015-03-10 /pmc/articles/PMC4496201/ /pubmed/25826087 Text en Copyright: © 2015 Ochoa-Alvarez 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 Research Paper
Ochoa-Alvarez, Jhon A.
Krishnan, Harini
Pastorino, John G.
Nevel, Evan
Kephart, David
Lee, Joseph J.
Retzbach, Edward P.
Shen, Yongquan
Fatahzadeh, Mahnaz
Baredes, Soly
Kalyoussef, Evelyne
Honma, Masaru
Adelson, Martin E.
Kaneko, Mika K.
Kato, Yukinari
Young, Mary Ann
Deluca-Rapone, Lisa
Shienbaum, Alan J.
Yin, Kingsley
Jensen, Lasse D.
Goldberg, Gary S.
Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms
title Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms
title_full Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms
title_fullStr Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms
title_full_unstemmed Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms
title_short Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms
title_sort antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496201/
https://www.ncbi.nlm.nih.gov/pubmed/25826087
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