Research Papers:

Oral inflammation promotes oral squamous cell carcinoma invasion

Cameron Goertzen, Hayder Mahdi, Catherine Laliberte, Tomer Meirson, Denise Eymael, Hava Gil-Henn and Marco Magalhaes _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2018; 9:29047-29063. https://doi.org/10.18632/oncotarget.25540

Metrics: PDF 2012 views  |   HTML 3858 views  |   ?  


Cameron Goertzen1, Hayder Mahdi1, Catherine Laliberte1,3, Tomer Meirson2, Denise Eymael1, Hava Gil-Henn2 and Marco Magalhaes1,3,4

1Cancer Invasion and Metastasis Laboratory, Faculty of Dentistry, University of Toronto, Toronto, Canada

2Cell Migration and Invasion Laboratory, Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel

3Oral Pathology and Oral Medicine, Faculty of Dentistry, University of Toronto, Toronto, Canada

4Sunnybrook Health Sciences Centre, Toronto, Canada

Correspondence to:

Marco Magalhaes, email: [email protected]

Keywords: cancer; metastasis; inflammation; neutrophils; TNF

Received: November 07, 2017     Accepted: May 07, 2018     Published: June 26, 2018


Oral squamous cell carcinoma (OSCC) represents 95% of oral malignancies and invasion, and metastasis underlies disease morbidity and mortality. We recently established a direct link between oral inflammation and cancer invasion by showing that neutrophils increase OSCC invasion through a tumor necrosis factor (TNFα)-dependent mechanism. The objective of this study was to characterize OSCC-associated inflammation and to determine the molecular mechanisms underlying inflammation-mediated OSCC invasion. Our results showed a significant increase in neutrophil infiltration, the neutrophil-to-lymphocyte ratio in the OSCC microenvironment and increased inflammatory markers, particularly TNFα in saliva. We performed next-generation sequencing of the TNFα-treated OSCC cells and showed marked overexpression of over 180 genes distributed among clusters related to neutrophil recruitment, invasion, and invadopodia. At the molecular level, TNFα treatment increased phosphoinositide 3-kinase (PI3K)-mediated invadopodia formation and matrix metalloproteinase (MMP)-dependent invasion. We show here that TNFα promotes a pro-inflammatory and pro-invasion phenotype leading to the recruitment and activation of inflammatory cells in a paracrine mechanism. Increased TNFα in the tumor microenvironment tips the balance towards invasion leading to decreased overall survival and disease-free survival. This represents a significant advancement of oral cancer research and will support new treatment approaches to control OSCC invasion and metastasis.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 25540