Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms.
Publication/Presentation Date
4-20-2015
Abstract
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.
Volume
6
Issue
11
First Page
9045
Last Page
9060
ISSN
1949-2553
Published In/Presented At
Ochoa-Alvarez, J. A., Krishnan, H., Pastorino, J. G., Nevel, E., Kephart, D., Lee, J. J., Retzbach, E. P., Shen, Y., Fatahzadeh, M., Baredes, S., Kalyoussef, E., Honma, M., Adelson, M. E., Kaneko, M. K., Kato, Y., Young, M. A., Deluca-Rapone, L., Shienbaum, A. J., Yin, K., Jensen, L. D., … Goldberg, G. S. (2015). Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms. Oncotarget, 6(11), 9045–9060. https://doi.org/10.18632/oncotarget.3515
Disciplines
Medicine and Health Sciences
PubMedID
25826087
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article