Neutrophils Increase Oral Squamous Cell Carcinoma Invasion through an Invadopodia-Dependent Pathway.

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.

Neutrophils and oral squamous cell carcinoma: lessons learned and future directions.

The role of cells of the innate immune system in the pathogenesis of squamous cell carcinoma has been the subject of intense research in recent years. In particular, neutrophils have been shown recently to have either a pro-tumor or anti-tumor phenotype in different cancers. Here, we review the role of neutrophils as tumor microenvironment and signaling modulators of OSCC and their possible role as biomarkers of OSCC prognosis. Current evidence supports a pro-tumor role for neutrophils in OSCC, but more research is needed to clarify the precise mechanisms involved.