Hyperthermia decreases cytokine-mediated adhesion molecule expression on human umbilical vein endothelial cells

Abstract

Although hyperthermia has been used as an effective cancer treatment modality, its effects on metastasis of tumour cells are not clear. Since adhesion molecules play a key role in metastasis, we evaluated how the expression of adhesion molecules is influenced by hyperthermia. Human umbilical vein endothelial cells were incubated in vitro for 1 h. at 39, 42, 43 and 44°C with and without addition of tumour-necrosis factor (TNF) or interferon-gamma (IFN-γ) and the expression of endothelial cell leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) class-II molecule was measured. Expression of MHC class-II molecules and expression of unstimulated constituent ICAM-1's was not reduced by heat treatment. In contrast, expression of cytokine-induced ELAM-1's and ICAM-1's was significantly lower after heat treatment. The adhesion 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°C and totally lost after treatment at 44°C. This suggests that any decrease in metastasis formation after heat treatment, which is occasionally observed, could be due to a reduced action of TNF or related cytokines on adhesion molecule induction and subsequent membrane expression by the endothelial cell. A possible underlying mechanism involved is a heat-induced alteration or blockage of the biosynthetic pathways required for synthesis of ELAM-1 and ICAM-1 proteins.

Key Words:

• hyperthermia
• adhesion molecules
• cytokines
• metastasis and endothelial cells