Intracellular calprotectin (S100A8/A9) controls epithelial differentiation and caspase-mediated cleavage of EGFR in head and neck squamous cell carcinoma.
Adult
Aged
Aged, 80 and over
Apoptosis
Calgranulin A
/ metabolism
Calgranulin B
/ metabolism
Caspase 3
/ metabolism
Caspase 7
/ metabolism
Cell Differentiation
Cell Line, Tumor
Epithelial Cells
/ pathology
ErbB Receptors
/ metabolism
Female
Gene Knockdown Techniques
Head and Neck Neoplasms
/ pathology
Humans
Leukocyte L1 Antigen Complex
/ genetics
Male
Middle Aged
Mouth Mucosa
/ cytology
Proteolysis
RNA, Small Interfering
/ metabolism
Squamous Cell Carcinoma of Head and Neck
/ mortality
Survival Rate
Young Adult
Calprotectin
Caspase-3/7
EGFR
Epithelial differentiation
Head and neck squamous cell carcinoma
NGF
P16+ squamous cell carcinoma
Premalignant epithelial dysplasia
S100A8/A9
VEGF-A
VEGF-C
Journal
Oral oncology
ISSN: 1879-0593
Titre abrégé: Oral Oncol
Pays: England
ID NLM: 9709118
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
27
11
2018
revised:
21
05
2019
accepted:
29
05
2019
entrez:
27
7
2019
pubmed:
28
7
2019
medline:
7
7
2020
Statut:
ppublish
Résumé
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. (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. 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. 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. 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.
Identifiants
pubmed: 31345374
pii: S1368-8375(19)30175-7
doi: 10.1016/j.oraloncology.2019.05.027
pmc: PMC6662626
mid: NIHMS1531591
pii:
doi:
Substances chimiques
Calgranulin A
0
Calgranulin B
0
Leukocyte L1 Antigen Complex
0
RNA, Small Interfering
0
S100A8 protein, human
0
S100A9 protein, human
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
CASP3 protein, human
EC 3.4.22.-
CASP7 protein, human
EC 3.4.22.-
Caspase 3
EC 3.4.22.-
Caspase 7
EC 3.4.22.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-10Subventions
Organisme : NIDCR NIH HHS
ID : R01 DE021206
Pays : United States
Organisme : NIDCR NIH HHS
ID : R90 DE023058
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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