gms | German Medical Science

Biopsies from carcinoma and benign mucosa from head and neck squamous cell carcinoma (HNSCC) patients have been used to establish fragment (F)-spheroids in vitro.

We have shown that autologous monocytes co-cultured with F-spheroids in vitro augment the secretion of monocyte chemo-tactic protein-1 (MCP-1). Co-culture of monocytes and F-spheroids separated by a semipermeable 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.

Addition of anti-CD14 antibody diminished the MCP-1 co-culture response.

Malignant (M) F-spheroids secrete more MCP-1 than benign (B) F-spheroids. No F-spheroids secreted measureable 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. There was also an association between MF- and BF-spheroid-stimulated monocytokine secretion, as well as between BF- and MF-spheroid-stimulated MCP-1 secretion. There was an inverse relation between ESR (erytrocyte sedimentation rate) and monocyte harvest and the monocyte MCP-1 F-spheroid responses.

The monocyte IL-6 co-culture response was dependent on live spheroids and to some extent on direct contact with F-spheroids, possibly via lectin-like receptor(s), the mannose receptor and beta-1-integrin.

Thus mononuclear phagocytes (MNP) function in HNSCC patients is more a functional entity that is related to the inflammatory state of the organism than previously recognized.

Studies on the molecular counterparts of the shown interactions such as the density of lectins/lectin receptors and additional receptors should probably shed further light on mononuclear function in HNSCC patients. If thorough understanding of these mechanisms can be achieved it may lead to a future cancer therapy based on a modulated interaction between tumour cells and the MNP system.

MCP-1 is a pluripotent monokine with the ability to stimulate potential tumour cytotoxic cells like T-lymphocytes and NK cells. Thus, the shown MCP-1 secretion supports that monocytes contribute to tumour cytotoxicity in vivo.

The results of stimulation of the FM- and FB-spheroids support that the monocyte MCP-1 secretion is governed by similar mechanisms.

It is of interest to know that if control conditions had not been in place, the monocyte cancer tissue would easily have been accepted as being a specific tumour tissue and monocyte interaction. The present experiments support that the shown monocyte response against tumour tissue is merely a general response when monocytes are exposed to epithelial cells. Such interactions do not ordinarily take place in vivo, but may be seen in wounds and within tumour tissue.

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. Thus manipulation of these receptors may provide a basis for increased efficiency of treatment based on the use of biological response modifiers like OK-432.