Mechanisms for monocyte activation in co-culture with autologous tumor spheroids

• Published in: Cellular immunology 2002-09, Vol.219 (1), p.11-21
• Main Authors: Olsnes, C, Heimdal, J.-H, Kross, K, Olofsson, J, Aarstad, H.J
• Format: Article
• Language: English
• Subjects: Activation; Animals; Antibodies - pharmacology; Carcinoma, Squamous Cell; Co-culture; Coculture Techniques; Culture Media - chemistry; Dactinomycin - pharmacology; Formaldehyde - pharmacology; Galactose - pharmacology; Glucose - pharmacology; Head and Neck Neoplasms; Humans; Integrin beta1 - immunology; Interleukin-6 - analysis; Interleukin-6 - biosynthesis; Lipopolysaccharides - pharmacology; Mannose - pharmacology; Mice; Monocyte; Monocytes - drug effects; Monocytes - immunology; Neoplasms; Polymerase Chain Reaction; Polymers - pharmacology; RNA, Messenger - analysis; Spheroids; Spheroids, Cellular - drug effects; Spheroids, Cellular - metabolism; Time Factors; β 1-Integrin
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/S0008-8749(02)00615-9

Biopsies from carcinoma tissue and benign control mucosa from head and neck squamous cell carcinoma patients were used to establish fragment (F)-spheroids in vitro. We have previously shown that autologous monocytes co-cultured with F-spheroids in vitro secrete interleukin (IL)-6 upon 24 h in co-culture. Presently, the aim was to study the mechanisms of this monocyte secretion. Paraformaldehyde (0.1% for 2 min) or actinomycin-D ( 1 μ g/ml for 24 h) pre-treatment of the F-spheroids abolished the monocyte IL-6 co-culture response. Addition of glucose (100 mM) or mannose (100 mM), and to some extent galactose (100 mM), but not fructose (100 mM) to the co-cultures, partly inhibited the monocyte IL-6 co-culture response, but such addition did not inhibit the in vitro monocyte lipopolysaccharide (LPS)-generated IL-6 secretion. When mannose was added to the co-cultures, monocyte IL-6 mRNA expression was eradicated in malignant co-cultures and reduced to a low level in benign co-cultures. Addition of mouse anti-human β 1-integrin (anti-CD29) antibody (2 μ g/ml) diminished the IL-6 co-culture response but not the monocyte LPS-generated IL-6 response. In conclusion, the monocyte IL-6 co-culture response is dependent on live spheroids and to some extent on direct contact with the F-spheroids, possibly via lectin-like receptor(s), the mannose receptor and β 1-integrin.