title: Neutrophils Increase Oral Squamous Cell Carcinoma Invasion through an Invadopodia-Dependent Pathway.
abstract: Neutrophils have recently been shown to promote invasion and correlate with a poor prognosis in different cancers, including head and neck squamous cell carcinomas. In this study, we analyze the effects of neutrophils in the invasion of oral squamous cell carcinoma (OSCC) using a combination of conditioned media, direct and indirect coculture of human peripheral blood neutrophils, and UMSCC47 cells (OSCC cell line). Invasion and matrix degradation were determined using a modified in vitro invasion assay and an invadopodia assay, respectively. UMSCC47 and neutrophil cocultures or conditioned media from cocultures increased UMSCC47 invasion, invadopodia formation, and matrix degradation. Further analysis revealed an increase in TNFα and IL8 in supernatants of cocultures compared with neutrophil or UMSCC47 cultures alone and that inhibition of TNFα and IL8 significantly decreased OSCC invasion. Our results show that neutrophils increase the invasiveness of OSCC through the activation of invadopodia and matrix degradation, suggesting a paracrine activation loop between the two cells. Importantly, the presence of neutrophils in the oral environment may modulate the clinical behavior of OSCC.
authors.affiliation: Matrix Dynamics group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Judah E
authors.initials: JE
authors.lastname: Glogauer
authors.affiliation: Matrix Dynamics group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Chun X
authors.initials: CX
authors.lastname: Sun
authors.affiliation: Oral Pathology and Oral Medicine, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Grace
authors.initials: G
authors.lastname: Bradley
authors.affiliation: Matrix Dynamics group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. Oral Pathology and Oral Medicine, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. marco.magalhaes@utoronto.ca.
authors.forename: Marco A O
authors.initials: MA
authors.lastname: Magalhaes
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D005109:Extracellular Matrix / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009504:Neutrophils / Q000502:physiology*; D000069261:Podosomes / Q000502:physiology*; D011379:Prognosis; D015398:Signal Transduction / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C508606:CXCL8 protein, human; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha