A potential link between desmoglein 3 and epidermal growth factor receptor in oral squamous cell carcinoma and its effect on cetuximab treatment efficacy

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.

Assessment of Oxidative Stress and Inflammatory Markers of Medical Importance in Oral Squamous Cell Carcinoma

“…Interlukin-6 is a multifunctional cytokine having a wide range of immunological activities, and it is also a potential mediator in the cancer development. It is known to promote proliferation of OSCC cell lines and on the other hand stabilizes the antibody inhibited growth in vivo (Minabe et al, 2019). OSCC patients were examined to determine the expression of IL-6 and IL-6 receptor.…”

Paradoxical Roles of Desmosomal Components in Head and Neck Cancer

“…In OSCC, there is a potential link between DSG3 and EGFR, and the expression of DSG3 was significantly increased after treatment with cetuximab, an inhibitor of EGFR. Furthermore, high calcium-associated DSG3 induction enhanced the efficacy of cetuximab in cetuximab-low-sensitive cell lines by up to 23% [92]. Differential expression analysis in oral leukoplakia (OL) tissues and OSCC tissues showed mild to severe loss of the DSG3/γcatenin complex and a transition from membranous to cytoplasmic expression, resulting in perinuclear aggregation, which was directly related to the grade of dysplasia [95].…”