Abstract
Biopsies from carcinoma tissue and benign control mucosa from head and neck squamous cell carcinoma (HNSCC) patients were used to establish fragment (F)-spheroids in vitro. We have previously shown that autologous monocytes co-cultured with F-spheroids in vitro augment their secretion of monocyte chemotactic protein-1 (MCP-1). Presently, the aims of the present work were to study whether the metabolic activity, secreted products and/or specific receptor/ligand on the surface of the F-spheroids and monocytes are necessary for stimulation of the monocyte MCP-1 secretion upon F-spheroid co-culture. Actinomycin D (1 μg/ml for 24 h) pre-treatment of the F-spheroids abolished the monocyte MCP-1 co-culture response. Co-culture of monocytes and F-spheroids separated by a semi-permeable membrane showed a decreased, but still present, monocyte MCP-1 co-culture response. Conditioned medium from F-spheroids stimulated allogenous monocytes to secrete MCP-1. The addition of glucose or galactose, but not mannose, to co-cultures partially inhibited the monocyte MCP-1 co-culture response. The addition of anti-CD14 antibody diminished the MCP-1 co-culture response. In conclusion, the monocyte MCP-1 co-culture response is dependent on metabolically active spheroids, secreted stimuli, and is augmented by direct contact with F-spheroids, possibly via lectin-like receptors and the CD14 receptor.
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Acknowledgements
We thank Dagny Ann Sandnes and Turid Tynning for excellent technical assistance, and the Medical Research Center, University of Bergen, for providing parts of the laboratory facility used in this study. The work has been supported by The Norwegian Cancer Society.
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Parts of this paper were presented at the Sixth International Conference on Head and Neck Cancer in Washington, D.C.
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Olsnes, C., Heimdal, JH., Kross, K.W. et al. Viable head and neck tumor spheroids stimulate in vitro autologous monocyte MCP-1 secretion through soluble substances and CD14/lectin-like receptors. Eur Arch Otorhinolaryngol 262, 953–960 (2005). https://doi.org/10.1007/s00405-004-0902-1
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DOI: https://doi.org/10.1007/s00405-004-0902-1