Head and neck squamous cell carcinoma spheroid- and monocyte spheroid-stimulated IL-6 and monocyte chemotactic protein-1 secretion are related to TNM stage, inflammatory state and tumor macrophage density

Kenneth W. Krossa, John-Helge Heimdala, Carla Olsnesa, Jan Olofssona & Hans Jørgen Aarstada*a Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital and Broegelmann Research Laboratory, University of Bergen, Bergen, Norway† Correspondence: Hans Jørgen Aarstad, Department of Otorhinolaryngology/Head and Neck Surgery, Haukeland University Hospital, NO-5021, Bergen, Norway, +47 55 972669, +47 55 972643 hans.aarstad@ore.uib.noPart of this work has been presented at the 6th International Conference on Head and Neck Cancer, 7–11 August 2004, Washington D.C., USA.ConclusionMonocyte fragment (F)-spheroid-stimulated and F-spheroid IL-6 and monocyte chemotactic protein (MCP)-1 secretion are related to inflammatory state, macrophage density and the TNM stage of patients with head and neck squamous cell carcinoma (HNSCC).ObjectiveFragment (F)-spheroids from HNSCC patients in vitro secrete and stimulate autologous monocytes to secrete IL-6 and MCP-1. The aim of this investigation was to study this cytokine secretion in relation to other cytokines, spheroid composition and host factors.Material and methodsIn series I (n=14) the densities of epithelial cells, fibroblasts and macrophages were determined in sections from F-spheroids and donor tissue. In series II (n=17) the TNM stage, donor inflammatory state, macrophage density and the secretion of F-spheroid- and monocyte F-spheroid-stimulated IL-6, MCP-1 and tumor necrosis factor (TNF)-α were determined.ResultsEpithelial cells were partly replaced by interstitial tissue during spheroid formation. Malignant (M) F-spheroids secreted more MCP-1 than benign (B) F-spheroids. No F-spheroid secreted measurable amounts of TNF-α. Monocytes secreted more IL-6 when co-cultured with MF- compared to BF-spheroids. Monocyte IL-6 MF- and MCP-1 MB-spheroid-stimulated secretion correlated with macrophage density. In addition, there was an association between MF- and BF-spheroid-stimulated monocyte cytokine secretion, as well as between BF- and MF-spheroid-stimulated MCP-1 secretion. An inverse relation was also noted between the erythrocyte sedimentation rate at monocyte harvest and the monocyte MCP-1 F-spheroid responses.