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Cigarette smoke extract induces oral squamous cell carcinoma cell invasion in a receptor for advanced glycation end‐products‐dependent manner
Author(s) -
Chapman Steven,
Mick Madison,
Hall Parker,
Mejia Camilo,
Sue Stephanie,
Abdul Wase Bihishta,
Nguyen Margaret A.,
Whisenant Evan C.,
Wilcox Shalene H.,
Winden Duane,
Reynolds Paul R.,
Arroyo Juan A.
Publication year - 2018
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/eos.12395
Subject(s) - rage (emotion) , glycation , downregulation and upregulation , receptor , chemistry , cancer research , microbiology and biotechnology , biology , biochemistry , neuroscience , gene
Oral squamous cell carcinoma ( OSCC ) affects approximately 30,000 people and is associated with tobacco use. Little is known about the mechanistic effects of second‐hand smoke in the development of OSSC . The receptor for advanced glycation end‐products ( RAGE ) is a surface receptor that is upregulated by second‐hand smoke and inhibited by semi‐synthetic glycosaminoglycan ethers ( SAGE s). Our objective was to determine the role of RAGE during cigarette smoke extract‐induced cellular responses and to use SAGE s as a modulating factor of Ca9‐22 OSCC cell invasion. Ca9‐22 cells were cultured in the presence or absence of cigarette smoke extract and SAGE s. Cell invasion was determined and cells were lysed for western blot analysis. Ras and nuclear factor of kappa light polypeptide gene enhancer in B‐cells ( NF ‐ κ B) activation were determined. Treatment of cells with cigarette smoke extract resulted in: (i) increased invasion of OSCC ; (ii) increased RAGE expression; (iii) inhibition of cigarette smoke extract‐induced OSCC cell invasion by SAGE s; (iv) increased Ras, increased AKT and NF ‐ κ B activation, and downregulation by SAGE s; and (v) increased expression of matrix metalloproteinases ( MMP s) 2, 9, and 14, and downregulation by SAGE s. We conclude that cigarette smoke extract increases invasion of OSCC cells in a RAGE ‐dependent manner. Inhibition of RAGE decreases the levels of its signaling molecules, which results in blocking the cigarette smoke extract‐induced invasion.