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

doi:10.1016/j.oraloncology.2018.09.030

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 journal › Article › peer-review

56 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 language	English
Pages (from-to)	251-257
Number of pages	7
Journal	Oral Oncology
Volume	86
DOIs	https://doi.org/10.1016/j.oraloncology.2018.09.030
Publication status	Published - Nov 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.oraloncology.2018.09.030

Cite this

@article{a125ee82680e42a1ac422a5079ea7e3d,

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

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.",

keywords = "Epidermal growth factor receptor, Epithelial-mesenchymal transition, Exosome, Extracellular vesicle, Head and neck cancer, Oral cancer",

author = "Toshifumi Fujiwara and Takanori Eguchi and Chiharu Sogawa and Kisho Ono and Jun Murakami and Soichiro Ibaragi and Asaumi, {Jun ichi} and Calderwood, {Stuart K.} and Kuniaki Okamoto and Ken-ichi Kozaｋi",

note = "Funding Information: This work was supported by JSPS KAKENHI , grant numbers JP17K11642 (to TE), 17K11643 (to CS TE), JP16K11722 (to JM TE), and JP17K11669 (to TE). Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",

year = "2018",

month = nov,

doi = "10.1016/j.oraloncology.2018.09.030",

language = "English",

volume = "86",

pages = "251--257",

journal = "Oral Oncology",

issn = "1368-8375",

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TY - JOUR

T1 - Carcinogenic epithelial-mesenchymal transition initiated by oral cancer exosomes is inhibited by anti-EGFR antibody cetuximab

AU - Fujiwara, Toshifumi

AU - Eguchi, Takanori

AU - Sogawa, Chiharu

AU - Ono, Kisho

AU - Murakami, Jun

AU - Ibaragi, Soichiro

AU - Asaumi, Jun ichi

AU - Calderwood, Stuart K.

AU - Okamoto, Kuniaki

AU - Kozaｋi, Ken-ichi

N1 - Funding Information: This work was supported by JSPS KAKENHI , grant numbers JP17K11642 (to TE), 17K11643 (to CS TE), JP16K11722 (to JM TE), and JP17K11669 (to TE). Publisher Copyright: © 2018 Elsevier Ltd

PY - 2018/11

Y1 - 2018/11

N2 - 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.

AB - 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.

KW - Epidermal growth factor receptor

KW - Epithelial-mesenchymal transition

KW - Exosome

KW - Extracellular vesicle

KW - Head and neck cancer

KW - Oral cancer

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JO - Oral Oncology

JF - Oral Oncology

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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