期刊
CANCER IMMUNOLOGY RESEARCH
卷 3, 期 11, 页码 1218-1226出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-15-0017
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资金
- Department of Oral Pathology and Oral Medicine of the Faculty of Dentistry, University of Toronto
- Javenthey Soobiah Scholarship
- Heidi Sternbach Scholarship, Postgraduate Medical Education, Faculty of Medicine
- Dental Research Institute
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 TNF alpha and IL8 in supernatants of cocultures compared with neutrophil or UMSCC47 cultures alone and that inhibition of TNF alpha 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. (C) 2015 AACR.
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