Cell to Cell Interaction in Clusters Enhances Thermosensitivity in HT29 Human Colon Cancer Cells

Background/Aims: Tumor cells at high density are considered to be resistant to hyperthermia. Our objective in this study was to investigate hyperthermia sensitivity of clusters, cancer cell aggregation, compared with that of monolayer cells. Methodology: Colon carcinoma cells HT29 were cultured on poly 2-hydroxyethyl methacrylate-coated dishes for 7 days and the clusters were selected by a 40 mu m pore filter. To detect the cell reproductive potential, a colony formation assay was performed in HT29 cells from a monolayer and from clusters after exposure to cis-diamino-dichloroplatinum, fluorouracil and/or hyperthermia. Western blotting was used to analyze the induction of heat shock protein expression by hyperthermia. Results: Histological findings of the clusters less than 400 mu m in diameter showed dividing cells and no secondary central necrosis. Cluster cells were more sensitive to hyperthermia than monolayer cells (p<0.0001). However, cluster formation induced cis-diamino-dichloroplatinum resistance (p<0.0001). The enhancement of hyperthermia sensitivity in clusters was not observed when the cells were heated after dispersion to single cells (p<0.0001). No difference of heat-induced HSP70/72 and HSP27 expression between cluster cells and monolayer cells was found. Conclusions: Cluster formation induced hyperthermia sensitivity, and cell-to-cell interaction in the clusters might enhance hyperthermia sensitivity.