title: 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 degrees C with and without addition of tumour-necrosis factor (TNF) or interferon-gamma (IFN-gamma) 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 degrees C and totally lost after treatment at 44 degrees 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.
authors.affiliation: Center of Applied Microcirculatory Research, University of Louisville, School of Medicine, KY 40292, USA.
authors.forename: K
authors.initials: K
authors.lastname: Brand
authors.forename: A S
authors.initials: AS
authors.lastname: Lübbe
authors.forename: D J
authors.initials: DJ
authors.lastname: Justus
mesh_terms: D002448:Cell Adhesion; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000378:metabolism*; D018922:HL-60 Cells; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D006979:Hyperthermia, Induced; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology*; D013696:Temperature; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D019040:E-Selectin; D000949:Histocompatibility Antigens Class II; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma