In vitro cytokine expression in in situ-like areas of malignant neoplasia.

Objectives: The myoepithelial cells exert important effects regulating the transition of an in situ to an invasive carcinoma. This cell has been associated with a tumour suppressor phenotype due to its ability to inhibit tumour growth as well as its immunomodulatory role in cancer behaviour.

Design: In order to correlate the cancer cell growth and the role of cytokines in regulating the neoplastic process, we have attempted to simulate an in vitro model of tumorigenesis, which mimics a situation where in situ neoplastic cells of carcinoma are surrounded by benign myoepithelial cells from pleomorphic adenoma. To certify the formation of in situ-like neoplasic areas, the cells were immunostained with vimentin and AE1/AE3, markers for tumoral benign myoepithelial cells and squamous cell carcinoma lineage, respectively. We investigated the correlation of the cancer cell growth with the releasing of IL-4, IL-6 and IL-10 associated with the immune response. The cytokines levels were evaluated using ELISA.

Results: In in situ neoplastic areas, IL-6 amounts were higher released when compared with IL-4 and IL-10, in all studied periods. Interestingly, the peak of IL-6 release fits with the predominance of malignant cells in the culture.

Conclusions: The present results demonstrated that, in this in vitro condition, the myoepithelial cells were not able to suppress the tumour cell proliferation even with high secretion of IL-4 by benign myoepithelial cells which at the beginning is supposed to act as an anti-tumour agent. In addition, these cells favoured the tumour growth by excessive production of IL-6 and IL-10.