Conditioned medium from HeLa cells enhances motility of human monocyte-derived dendritic cells but abrogates their maturation and endocytic activity.
Progressive tumor proliferation may be associated with suppression of the immune response. Several different mechanisms can contribute to immune evasion. It is generally proposed that inhibition of dendritic cell functions would be a key mechanism by which tumors could escape immune surveillance. Therefore, the purpose of this study was to evaluate the capacity of HeLa cells conditioned medium (HeLa-CM) to modulate phenotypic and functional parameters of human peripheral blood monocyte-derived dendritic cells (DCs). Two types of reference DCs population were generated in vitro, the first cultured in the presence of IL-4 and GM-CSF which represented immature DCs (iDCs) and the second, representing mature DCs (mDCs), was raised from the iDCs by additional stimulation with a maturation cocktail - TNF-alpha, IL-1beta, IL-6, PGE2. In parallel, the iDCs were treated with HeLa-CM collected from the tumor cells. The analysis of DC populations demonstrated that the HeLa-CM prevented maturation of these cells and also impaired their capacity to uptake an antigen and stimulate proliferation of allogeneic T cells. In contrast, HeLa-CM modulated DCs exhibited a 3-fold increase mobility over iDCs. The latter functional capacity did not correlate with the levels of matrix metalloproteinase expression in the analysed cells. Altogether, our results provide evidence that HeLa cells produce soluble factors that might dramatically alter basic phenotypic and functional characteristics of DCs.
Kúdela
P
P
Department of Tumor Cell Biology, Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Schwarczová
Z
Z
Sedlák
J
J
Bizik
J
J
D002465:Cell Movement; D002469:Cell Separation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D016130:Immunophenotyping; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010641:Phenotype
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free