title: 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.
abstract: Monocyte 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). Fragment (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.In 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)-alpha were determined. Epithelial 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-alpha. 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.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital and Broegelmann Research Laboratory, University of Bergen, Bergen, Norway.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kross
authors.forename: John-Helge
authors.initials: JH
authors.lastname: Heimdal
authors.forename: Carla
authors.initials: C
authors.lastname: Olsnes
authors.forename: Jan
authors.initials: J
authors.lastname: Olofsson
authors.forename: Hans Jørgen
authors.initials: HJ
authors.lastname: Aarstad
mesh_terms: D001799:Blood Sedimentation; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D018932:Chemokine CCL2 / Q000378:metabolism*; D018920:Coculture Techniques; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008264:Macrophages; D009000:Monocytes / Q000378:metabolism*; D009367:Neoplasm Staging; D018874:Spheroids, Cellular / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha