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

• Published in: Oncotarget 2015-04, Vol.6 (11), p.9045-9060
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Animals, Genetically Modified; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Cell Line, Tumor; Cell Movement - drug effects; Cell Survival - drug effects; Fibroblasts - pathology; Humans; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - immunology; Membrane Glycoproteins - physiology; Membrane Potential, Mitochondrial - drug effects; Mice; Molecular Targeted Therapy; Mouth Neoplasms - pathology; Mouth Neoplasms - virology; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - immunology; Neoplasm Proteins - physiology; Papillomaviridae - isolation & purification; Papillomavirus Infections - pathology; Papillomavirus Infections - virology; Phytohemagglutinins - administration & dosage; Phytohemagglutinins - pharmacology; Phytohemagglutinins - therapeutic use; Research Paper; Xenograft Model Antitumor Assays; Zebrafish - embryology
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.3515

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.