title: Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms.
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.
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: Jhon A
authors.initials: JA
authors.lastname: Ochoa-Alvarez
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: Harini
authors.initials: H
authors.lastname: Krishnan
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Pastorino
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Nevel
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kephart
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Retzbach
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Fatahzadeh
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA.
authors.forename: Soly
authors.initials: S
authors.lastname: Baredes
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Kalyoussef
authors.affiliation: Department of Dermatology, Asahikawa Medical University, Midorigaoka-Higashi, Asahikawa, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Honma
authors.affiliation: Medical Diagnostic Laboratories, Hamilton, NJ, USA.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Adelson
authors.affiliation: Department of Regional Innovation, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Mika K
authors.initials: MK
authors.lastname: Kaneko
authors.affiliation: Department of Regional Innovation, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Young
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Deluca-Rapone
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Shienbaum
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: Kingsley
authors.initials: K
authors.lastname: Yin
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Lasarettsgatan, Ingång, Linköping, Sweden.
authors.forename: Lasse D
authors.initials: LD
authors.lastname: Jensen
authors.affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Goldberg
mesh_terms: D000284:Administration, Oral; D000818:Animals; D030801:Animals, Genetically Modified; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D058990:Molecular Targeted Therapy; D009062:Mouth Neoplasms / Q000473:pathology* / Q000821:virology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology; D010835:Phytohemagglutinins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish / Q000196:embryology; D000098853:Podoplanin
chemical_list: D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010835:Phytohemagglutinins; C117468:PDPN protein, human; D000098853:Podoplanin; C100156:leukoagglutinins, plants
keywords: cancer; cell migration; lectin; podoplanin; receptor
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