Carcinogenic epithelial-mesenchymal transition initiated by oral cancer exosomes is inhibited by anti-EGFR antibody cetuximab

Toshifumi Fujiwara, Takanori Eguchi, Chiharu Sogawa, Kisho Ono, Jun Murakami, Soichiro Ibaragi, Jun-Ichi Asaumi, Stuart K. Calderwood, Kuniaki Okamoto, Ken ichi Kozaki

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Overexpression and increased signaling from the epidermal growth factor receptor (EGFR) often changes oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed the roles of OSCC-derived extracellular vesicles (EVs), including exosomes in the trafficking of cetuximab and in epithelial-mesenchymal transition (EMT) of epithelial cells. OSCC cells abundantly expressed EGFR, which was secreted from cells with OSCC-EVs upon EGF stimulations. The OSCC-EGFR-EVs were then able to enter into and transform epithelial cells leading to increased mesenchymal traits with increased vimentin and spindle-like shapes. EGF priming of OSCC cells further increased this EMT-initiating effect of the OSCC-EVs. The internalization and pro-EMT effects of the OSCC-EVs were largely blocked by cetuximab. Thus, OSCC-derived EVs transform normal epithelial cells into a mesenchymal phenotype and anti-EGFR therapeutic antibody cetuximab inhibits such a carcinogenic effect of the OSCC-EVs.

Original languageEnglish
Pages (from-to)251-257
Number of pages7
JournalOral Oncology
Volume86
DOIs
Publication statusPublished - Nov 1 2018

Keywords

  • Epidermal growth factor receptor
  • Epithelial-mesenchymal transition
  • Exosome
  • Extracellular vesicle
  • Head and neck cancer
  • Oral cancer

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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