Three-dimensional culture and multidrug resistance: effects on immune reactivity of MCF-7 cells by monocytes.

ABSTRACT

BACKGROUND: Multicellular spheroids are known to be the most adapted model to keep the in vitro resistance properties of cells. This in vivo-like tissue-culture representation was applied to investigate the immune reactivity of MCF-7 cells by monocytes. MATERIALS AND METHODS: Human blood monocytes, obtained by elutriation, were co-cultured with multicellular tumor spheroids of drug-sensitive (MCF-7S) and doxorubicin-resistant (MCF-7DXR) MCF-7 breast cancer cells. RESULTS: Tumor cells, according to their phenotype, induced differential recruitment and behavior of the immune cells towards the two types of spheroids. The secretion of various cytokines and the expression of several adhesion molecules were analysed. The MCF-7DXR/monocytes co-culture supernatant showed higher levels of IL-6 and IL-8 than the MCF-7S/monocytes co-culture supernatant. Cells from the MCF-7DXR spheroids expressed some adhesion molecules, CD-44 and CD-54, leading to a strong cellular cohesion in comparison with the sensitive spheroids. CONCLUSION: The two spheroid phenotypes represented an excellent model system for determining the precise tumor microenvironment in which cells move, the crucial molecular requirements and the mechanisms by which immunotherapeutic strategies could be developed to eradicate chemo-resistant tumors.