Ovarian cancer cells induce peripheral mature dendritic cells to differentiate into macrophagelike cells in vitro.

AIMS

Precursors of dendritic cells (DCs) are able to differentiate into macrophages induced by some tumor-associated molecules; however, whether peripheral mature DCs could differentiate into macrophages remains unknown. This study was designed to find out whether ovarian cancer cells could induce peripheral mature DCs to differentiate into macrophages.

MAIN METHODS

Mature DCs were cultured from monocytes with granulocyte-macrophage colony-stimulating factor and interleukin 4 (IL-4) for 6 days and lipopolysaccharide for another 24 hours and then were cocultured for 48 hours with ovarian cancer ascites or cell-free supernatants of SKOV3 and CAOV3 cell lines. In some experiments, mature DCs were cultured in the absence or presence of IL-10 or leukemia inhibitory factor (LIF) for the same time. In neutralization experiments, neutralizing monoclonal antibodies to IL-10 or LIF were added to the cultures. Cell phenotypes and phagocytosis were analyzed using flow cytometry; allogeneic T-cell proliferation assay was used to examine stimulatory activity of cells.

RESULTS AND CONCLUSIONS

Mature DCs cocultured with ovarian cancer ascites or supernatants of SKOV3 and CAOV3 differentiated into a group of macrophagelike cells that exhibited increased expression of surface marker CD14+CD1a-, decreased expression of CD83, poorer T-cell costimulatory properties, and greater endocytosis of fluorescein isothiocyanate-dextran in vitro. Interleukin 10 but not LIF mediated this differentiation pathway.