Anti-EGFR antibody cetuximab is secreted by oral squamous cell carcinoma and alters EGF-driven mesenchymal transition

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance.

Original languageEnglish
JournalBiochemical and Biophysical Research Communications
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Epidermal Growth Factor Receptor
Epidermal Growth Factor
Squamous Cell Carcinoma
Antibodies
Cetuximab
Epithelial Cells
Amplification

Keywords

  • Anti-EGFR antibody therapy
  • Cetuximab
  • Epithelial-to-mesenchymal transition
  • Extracellular vesicles
  • Head and neck squamous cell carcinoma

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{09c849a5c2464e769a78666e4bb71ad3,
title = "Anti-EGFR antibody cetuximab is secreted by oral squamous cell carcinoma and alters EGF-driven mesenchymal transition",
abstract = "Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance.",
keywords = "Anti-EGFR antibody therapy, Cetuximab, Epithelial-to-mesenchymal transition, Extracellular vesicles, Head and neck squamous cell carcinoma",
author = "Toshifumi Fujiwara and Takanori Eguchi and Chiharu Sogawa and Kisho Ono and Jun Murakami and Soichiro Ibaragi and Jun-Ichi Asaumi and Kuniaki Okamoto and Calderwood, {Stuart K.} and Kozaki, {Ken ichi}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.bbrc.2018.07.035",
language = "English",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Anti-EGFR antibody cetuximab is secreted by oral squamous cell carcinoma and alters EGF-driven mesenchymal transition

AU - Fujiwara, Toshifumi

AU - Eguchi, Takanori

AU - Sogawa, Chiharu

AU - Ono, Kisho

AU - Murakami, Jun

AU - Ibaragi, Soichiro

AU - Asaumi, Jun-Ichi

AU - Okamoto, Kuniaki

AU - Calderwood, Stuart K.

AU - Kozaki, Ken ichi

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance.

AB - Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance.

KW - Anti-EGFR antibody therapy

KW - Cetuximab

KW - Epithelial-to-mesenchymal transition

KW - Extracellular vesicles

KW - Head and neck squamous cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85049759912&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049759912&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2018.07.035

DO - 10.1016/j.bbrc.2018.07.035

M3 - Article

C2 - 30017201

AN - SCOPUS:85049759912

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

ER -