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
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 The Author(s)
PY - 2018/9/10
Y1 - 2018/9/10
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
SN - 0006-291X
VL - 503
SP - 1267
EP - 1272
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -