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

Jhon A. Ochoa-Alvarez, Harini Krishnan, John G. Pastorino, Evan Nevel, David Kephart, Joseph J. Lee, Edward P. Retzbach, Yongquan Shen, Mahnaz Fatahzadeh, Soly Baredes, Evelyne Kalyoussef, Masaru Honma, Martin E. Adelson, Mika K. Kaneko, Yukinari Kato, Mary Ann Young, Lisa Deluca-Rapone, Alan J. Shienbaum, Kingsley Yin, Lasse D. JensenGary S. Goldberg

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9045-9060
Number of pages16
JournalOncotarget
Volume6
Issue number11
DOIs
Publication statusPublished - 2015

Keywords

  • Cancer
  • Cell migration
  • Lectin
  • Podoplanin
  • Receptor

ASJC Scopus subject areas

  • Oncology

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