HYPERTHERMIA DECREASES CYTOKINE-MEDIATED ADHESION MOLECULE EXPRESSIONON HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

Although hyperthermia has been used as an effective cancer treatment m odality, its effects on metastasis of tumour cells are not clear. Sinc e adhesion molecules play a key role in metastasis: we evaluated how t he expression of adhesion molecules is influenced by hyperthermia. Hum an umbilical vein endothelial cells were incubated in vitro for 1 h. a t 39, 42, 43 and 44 degrees C with and without addition of tumour-necr osis factor (TNF) or interferon-gamma (IFN-gamma) and the expression o f endothelial cell leukocyte adhesion molecule-1 (ELAM-1), intercellul ar adhesion molecule-1 (ICAM-1) and major histocompatibility complex ( MHC) class-II molecule was measured. Expression of MHC class-II molecu les and expression of unstimulated constituent ICAM-1's was not reduce d by heat treatment. In contrast, expression of cytokine-induced ELAM- 1's and ICAM-1's was significantly lower after heat treatment. The adh esion to HUVEC in vitro of HL-60 leukemia cells, which express sialyl- Lewis-x antigen as a ligand to ELAM-1, was diminished after incubation at 42 degrees C and totally lost after treatment at 44 degrees C. Thi s suggests that any decrease in metastasis formation after heat treatm ent, which is occasionally observed, could be due to a reduced action of TNF or related cytokines on adhesion molecule induction and subsequ ent membrane expression by the endothelial cell. A possible underlying mechanism involved is a heat-induced alteration or blockage of the bi osynthetic pathways required for synthesis of ELAM-1 and ICAM-1 protei ns.