Tumour vascular endothelial growth factor (VEGF) mRNA in relation to serum VEGF protein levels and tumour progression in human renal cell carcinoma

2003 ◽  
Vol 31 (5) ◽  
pp. 335-340 ◽  
Author(s):  
B�rje Ljungberg ◽  
Jan Jacobsen ◽  
Stina H�ggstr�m-Rudolfssson ◽  
Torgny Rasmuson ◽  
Gudrun Lindh ◽  
...  
2009 ◽  
Vol 31 (3) ◽  
pp. 179-190
Author(s):  
Dennis Fontijn ◽  
Linda J. W. Bosch ◽  
Monique C. A. Duyndam ◽  
Maria P. A. van Berkel ◽  
Maarten L. Janmaat ◽  
...  

Background: 1F6 human melanoma xenografts overexpressing either the 18 kD (18kD) form or all (ALL) forms of human basic fibroblast growth factor (bFGF) demonstrate an abundant number of microvessels and accelerated growth. We now examined whether bFGF mediates vascular endothelial growth factor (VEGF) expression.Methods: Quantitative RT-PCR was used to determine bFGF and VEGF mRNA, VEGF protein secretion was measured by ELISA and VEGF promoter activation was assessed by a dual luciferase activity assay. Western blot was carried out to detect phosphorylation of bFGF-regulated target proteins.Results: In 1F6-18kD and 1F6-ALL clones VEGF mRNA was increased 4- to 5-fold and VEGF protein secretion was highly stimulated due to activation of the VEGF promotor. PI-3K, p38 MAPK and ERK1/2 MAPK pathways were activated, while inhibition of PI-3K or p38 resulted in, respectively, 55% and up to 70% reduction of VEGF mRNA overexpression. A concurrent 60% decrease in VEGF protein secretion was mostly apparent upon inhibition of PI-3K. Inhibition of ERK1/2 hardly affected VEGF mRNA or protein secretion. Two unselected human melanoma cell lines with high metastatic potential contained high bFGF and VEGF, while three non- or sporadically metastatic cell lines displayed low bFGF and VEGF.Conclusion: These data indicate that stimulation of VEGF protein secretion in response to bFGF overexpression may contribute to increased vascularization and enhanced aggressiveness in melanoma.


2000 ◽  
Vol 83 (06) ◽  
pp. 949-955 ◽  
Author(s):  
Hiroyuki Itaya ◽  
Satoki Nasu ◽  
Hidemi Yoshida ◽  
Yuki Matsubara ◽  
Koji Fujimoto ◽  
...  

SummaryVascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells. We studied the production of VEGF by human umbilical vein endothelial cells (HUVEC) and smooth muscle cells (SMC) in response to the stimulation with interleukin-1α (IL-1α). HUVEC expressed VEGF mRNA in response to IL-1α in doseand time-dependent manners. In HUVEC VEGF protein was detected only in cell lysates whereas in SMC most of the VEGF protein was detected in the conditioned medium. Immunofluorescent staining also confirmed the cell-associated VEGF in HUVEC. IL-1α also induced the expression of mRNA for IL-1α itself in HUVEC. Cycloheximide treatment of HUVEC slightly inhibited the IL-1α-induced expression of VEGF mRNA, and IL-1α may mediate, at least in part, VEGF expression in response to IL-1α. The growth of HUVEC stimulated with IL-1α was inhibited by a neutralizing antibody against VEGF. We conclude that IL-1α and VEGF may play an important role in autocrine growth regulation of HUVEC.


2003 ◽  
Vol 285 (4) ◽  
pp. H1759-H1763 ◽  
Author(s):  
N. Hiscock ◽  
C. P. Fischer ◽  
H. Pilegaard ◽  
B. K. Pedersen

Angiogenesis, the growth of new blood vessels from existing ones, occurs in the skeletal muscle as an adaptive response to exercise that satisfies the increased requirement of this tissue for oxygen delivery and metabolic processes. Of the factors that have been identified to regulate this process, the endothelial cell mitogen vascular endothelial growth factor (VEGF) has been proposed to play a key role. The aim of this study was to measure the skeletal muscle VEGF mRNA content and arteriovenous protein balance across the working leg in response to a single bout of prolonged, submaximal exercise. Seven physically active males completed 3 h of two-legged kicking ergometry. Muscle biopsies were collected from the vastus lateralis muscle from both working legs, and blood samples were collected from one femoral artery and femoral vein before, during, and in recovery from exercise. We show that the exercise stimulus elicited a decrease in VEGF protein arteriovenous balance across the exercising leg ( P = 0.007), and a ninefold elevation in skeletal muscle VEGF mRNA expression ( P < 0.001). The changes in VEGF protein balance and mRNA content were most pronounced 1 h after the cessation of exercise. In conclusion, these findings demonstrate that submaximal exercise, suitable for humans with low CV fitness, induces a decrease in VEGF arteriovenous balance that is likely to be of clinical significance in promoting angiogenic effects.


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