PUBLICATION
Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms
- Authors
- 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.
- ID
- ZDB-PUB-150401-2
- Date
- 2015
- Source
- Oncotarget 6(11): 9045-60 (Journal)
- Registered Authors
- Keywords
- cancer, cell migration, lectin, podoplanin, receptor
- MeSH Terms
-
- Zebrafish/embryology
- Neoplasm Proteins/antagonists & inhibitors*
- Neoplasm Proteins/immunology
- Neoplasm Proteins/physiology
- Molecular Targeted Therapy*
- Antibodies, Monoclonal/immunology
- Antibodies, Monoclonal/pharmacology*
- Antibodies, Monoclonal/therapeutic use
- Cell Survival/drug effects
- Phytohemagglutinins/administration & dosage
- Phytohemagglutinins/pharmacology*
- Phytohemagglutinins/therapeutic use
- Papillomaviridae/isolation & purification
- Animals, Genetically Modified
- Administration, Oral
- Fibroblasts/pathology
- Membrane Glycoproteins/antagonists & inhibitors*
- Membrane Glycoproteins/immunology
- Membrane Glycoproteins/physiology
- Cell Line, Tumor
- Carcinoma, Squamous Cell/pathology*
- Carcinoma, Squamous Cell/virology
- Cell Movement/drug effects
- Animals
- Mouth Neoplasms/pathology*
- Mouth Neoplasms/virology
- Xenograft Model Antitumor Assays
- Papillomavirus Infections/pathology
- Papillomavirus Infections/virology
- Mice
- Membrane Potential, Mitochondrial/drug effects
- Antineoplastic Agents, Phytogenic/administration & dosage
- Antineoplastic Agents, Phytogenic/pharmacology*
- Antineoplastic Agents, Phytogenic/therapeutic use
- Humans
- PubMed
- 25826087 Full text @ Oncotarget
Citation
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):9045-60.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping