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A potential link between desmoglein 3 and epidermal growth factor receptor in oral squamous cell carcinoma and its effect on cetuximab treatment efficacy
Author(s) -
Minabe Masaki,
Akiyama Yurie,
Higa Kazunari,
Tachikawa Tetsuhiko,
Takahashi Shinichi,
Nomura Takeshi,
Kouno Michiyoshi
Publication year - 2019
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13920
Subject(s) - cetuximab , epidermal growth factor receptor , desmoglein 3 , cancer research , medicine , egfr inhibitors , epidermal growth factor , oncology , receptor , immunology , cancer , antibody , colorectal cancer , autoimmune disease
Abstract Desmoglein (DSG) 3 is overexpressed in oral squamous cell carcinoma (OSCC). Epidermal growth factor receptor (EGFR) inhibitor cetuximab is widely used for OSCC treatment. Several evidences suggest a correlation between DSG3 and EGFR in epidermal keratinocytes. EGFR inhibition has been shown to enhance cell‐cell adhesion and induce terminal differentiation in epidermal cells. Thus, here we investigated the DSG3‐EGFR interaction in OSCC and its effect on cetuximab treatment. Cell lines established from the primary tumor and metastatic lymph nodes of four OSCC patients and three commercial OSCC cell lines were used for the experiments. Cells from metastatic lymph nodes of each patient expressed increased DSG3 and EGFR than cells from the primary tumor in the same patient. Cetuximab treatment increased DSG3 expression by up to 3.5‐fold in seven of the 11 cell lines. A high calcium concentration increased the expression of DSG3 and EGFR in a dose‐dependent manner. Strikingly, a high calcium‐associated DSG3 induction enhanced cetuximab efficacy by up to 23% increase in cetuximab‐low‐sensitive cell lines. Our findings also suggest a correlation between DSG3 and EGFR in OSCC, and this affects cetuximab treatment efficacy.