Anti-angiogenic action of hyperthermia by suppressing gene expression and production of tumour-derived vascular endothelial growth factor in vivo and in vitro.
Bottom Line: The gene expression of alternative splicing variants for vascular endothelial growth factor, VEGF121, VEGF165 and VEGF189, was constitutively detected in HT-1080 cells, but the VEGF189 transcript was less abundant than VEGF121 and VEGF165.On the other hand, HT-1080 cell-conditioned medium showed vascular endothelial growth factor-dependent cell proliferative activity and the augmentation of pro-matrix metalloproteinase-1 production in human umbilical vein endothelial cells.The augmentation of endothelial-cell proliferation and pro-matrix metalloproteinase-1 production was poor when human umbilical vein endothelial cells were treated with conditioned medium from heat-shocked HT-1080 cells.
Affiliation: Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.Show MeSH
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Mentions: The augmentation of proteolytic activity is crucial for extracellular matrix (ECM) remodelling in order to provide a permissive environment in which activated endothelial cells can proliferate and form new vessels (Moses, 1997; Liotta et al, 1991). In addition, endothelial MMPs such as MMP-1 and MT1-MMP have been shown to participate in ECM remodelling in the perivascular environment (Fisher et al, 1994; Hiraoka et al, 1998). We therefore investigated the effect of conditioned medium from HT-1080 cells on the production of proMMP-1 in HUVECs. Western blot analysis showed that the production of proMMP-1 in HUVEC was augmented by the conditioned medium from HT-1080 cells (6.2-fold) as well as by recombinant human VEGF165 (4.2-fold) (Figure 7AFigure 7
Affiliation: Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.