Intracellular calprotectin (S100A8/A9) controls epithelial differentiation and caspase-mediated cleavage of EGFR in head and neck squamous cell carcinoma

Autor: Betty Pakzad, Ketan Patel, Mark C. Herzberg, Deepak Kademani, Ali Khammanivong, Ioannis G. Koutlas, Chris Malz, Prokopios P. Argyris, Zachary M. Slama
Rok vydání: 2018
Předmět:
Adult
Male
Cancer Research
Cellular differentiation
Apoptosis
medicine.disease_cause
Article
S100A8
03 medical and health sciences
Young Adult
0302 clinical medicine
Cell Line
Tumor
Carcinoma
medicine
Calgranulin B
Humans
Calgranulin A
Epidermal growth factor receptor
RNA
Small Interfering
030223 otorhinolaryngology
Aged
Aged
80 and over
Caspase 7
biology
business.industry
Caspase 3
Squamous Cell Carcinoma of Head and Neck
Mouth Mucosa
Cell Differentiation
Epithelial Cells
Middle Aged
medicine.disease
Head and neck squamous-cell carcinoma
ErbB Receptors
Survival Rate
Oncology
Head and Neck Neoplasms
030220 oncology & carcinogenesis
Gene Knockdown Techniques
Proteolysis
Cancer research
biology.protein
Immunohistochemistry
Female
Oral Surgery
Calprotectin
business
Carcinogenesis
Leukocyte L1 Antigen Complex
Zdroj: Oral Oncol
ISSN: 1879-0593
Popis: Objectives Calprotectin (S100A8/A9) appears to function as a tumor suppressor in head and neck squamous cell carcinoma (HNSCC) and expression in the carcinoma cells and patient survival rates are directly related. We seek to characterize the suppressive role of calprotectin in HNSCC. Aims (1) Investigate changes in S100A8/A9 expression as oral carcinogenesis progresses and (2) determine whether intracellular calprotectin can regulate epidermal growth factor receptor (EGFR), a negative prognostic factor, in HNSCC. Materials and methods Using immunohistochemistry (IHC), S100A8/A9 was analyzed in HNSCC specimens (N = 46), including well-differentiated (WD, N = 19), moderately-differentiated (MD, N = 14), poorly-differentiated (PD, N = 5) and non-keratinizing/basaloid (NK/BAS, N = 8), and premalignant epithelial dysplasias (PED, N = 16). Similarly, EGFR was analyzed in HNSCCs (N = 21). To determine whether calprotectin and EGFR expression are mechanistically linked, TR146 HNSCC cells that are S100A8/A9-expressing or silenced (shRNA) were compared for EGFR levels and caspase-3/7 activity using western blotting and immunofluorescence microscopy. Results In normal oral mucosal epithelium, S100A8/A9 stained strongly in the cytoplasm and nucleus of suprabasal cells; basal cells were consistently S100A8/A9 negative. In PED and HNSCC, S100A8/A9 expression was lower than in adjacent normal epithelial tissues (NAT) and declined progressively in WD, MD, PD and NK/BAS HNSCCs. S100A8/A9 and EGFR levels appeared inversely related, which was simulated in vitro when S100A8/A9 was silenced in TR146 cells. Silencing S100A8/A9 significantly reduced caspase-3/7 activity, whereas EGFR levels increased. Conclusions In HNSCC, S100A8/A9 is directly associated with cellular differentiation and appears to promote caspase-3/7-mediated cleavage of EGFR, which could explain why patients with S100A8/A9-high tumors survive longer.
Databáze: OpenAIRE
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