Neopterin as a Stimulator of Vascular Endothelial Growth Factor and Erythropoietin Gene Expression in an Ovarian Carcinoma Cell Line

Pteridines ◽  
2005 ◽  
Vol 16 (4) ◽  
pp. 166-173 ◽  
Author(s):  
Josef Rieder ◽  
Christian Marth ◽  
Wolfgang Schobersberger ◽  
Georg Hoffmann
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Ovarian Carcinoma ◽  
Cell Line ◽  
Carcinoma Cell ◽  
Vascular Endothelial ◽  
Ovarian Carcinoma Cell Line ◽  
Endothelial Growth Factor ◽  
Stimulation Of

Abstract Increases in serum neopterin concentrations are a regular finding in patients with ovarian cancer. The strong correlation between neopterin and tumor progression might be explained by a direct influence of the pteridine compound on tumor cell growth. In the present study we investigated whether neopterin affects the production of the angiogenic promotors vascular endothelial growth factor (VEGF) and erythropoietin (EPO) in the human ovarian carcinoma cell line OVCAR-3. VEGF and EPO gene expression were detected via RT-PCR. and a possible involvement of hypoxiainducible factor-1 was assessed by electrophoretic mobility shift assays. Neopterin amplified the hypoxia-induced VEGF and EPO gene expression as well as protein synthesis in a concentration-dependent manner. In addition, generation of both VEGF and EPO could be detected following incubation of cells with neopterin under normoxic conditions, too. Neopterin-induced synthesis of VEGF and EPO was preceeded by a stimulation of hypoxiainducible factor-1 uptake into the nucleus of OVCAR-3 cells. From these data we conclude that neopterin acts as a mediator of angiogenesis. Stimulation of VEGF and EPO generation in ovarian carcinoma cells may promote vascularization of the malignant tissue and thus tumor growth and development.

Tumor-induced endothelial cell activation: role of vascular endothelial growth factor

2004 ◽  
Vol 286 (5) ◽  
pp. C1170-C1176 ◽  
Author(s):  
M. Ángeles Castilla ◽  
Fernando Neria ◽  
Guadalupe Renedo ◽  
Daniel S. Pereira ◽  
Francisco R. González-Pacheco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Protein Kinase ◽  
Cell Line ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Osteoblastic Cell Line ◽  
Endothelial Growth Factor

Proangiogenic, proliferative effects of tumors have been extensively characterized in subconfluent endothelial cells (EC), but results in confluent, contact-inhibited EC are critically lacking. The present study examined the effect of tumor-conditioned medium (CM) of the malignant osteoblastic cell line MG63 on monolayer, quiescent bovine aorta EC. MG63-CM and MG63-CM + CoCl2 significantly increased EC survival in serum-starved conditions, without inducing EC proliferation. Furthermore, MG63-CM and MG63-CM + CoCl2, both containing high amounts of vascular endothelial growth factor (VEGF), induced relevant phenotypic changes in EC (all P < 0.01) involving increase of nucleoli/chromatin condensations, nucleus-to-cytosol ratio, capillary-like vacuolated structures, vessel-like acellular areas, migration through Matrigel, growth advantage in reseeding, and factor VIII content. All these actions were significantly inhibited by VEGF and VEGF receptor (VEGFR2) blockade. Of particular importance, a set of similar effects were detected in a human microvascular endothelial cell line (HMEC). With regard to gene expression, incubation with MG63-CM abolished endogenous VEGF mRNA and protein but induced a clear-cut increase in VEGFR2 mRNA expression in EC. In terms of mechanism, MG63-CM activates protein kinase B (PKB)/Akt, p44/p42-mitogen-activated protein kinase (MAPK)-mediated pathways, as suggested by both inhibition and phosphorylation experiments. In conclusion, tumor cells activate confluent, quiescent EC, promoting survival, phenotypic, and gene expression changes. Of importance, VEGF antagonism converts MG63-CM from protective to EC-damaging effects.

scholarly journals Effect of directly acting anti-viral agents on immunological imprints in chronic HCV-4a patients: interleukin-10 and vascular endothelial growth factor genes expression level

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iman S. Naga ◽  
Amel Abdel Fattah Kamel ◽  
Said Ahmed Ooda ◽  
Hadeer Muhammad Fath Elbab ◽  
Rania Mohamed El-Sharkawy
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Growth Factor ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Wide Range ◽  
Chronic Hcv ◽  
Endothelial Growth Factor

Abstract Background Hepatitis C virus infection is a global health challenge with Egypt being one of the highly affected countries. IL-10 has been suggested as a suitable marker to assess necroinflammation and to monitor the progression of liver damage. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor playing a central role in many physiological as well as pathological processes. Several factors can be predictive of the response to treatment and achievement of SVR; some of which are host-related, and others are virus-related. The gene expression of IL-10 and VEGF have multiple effects for treatment response. The aim of the present work was to study the effect of treatment with directly acting agents (DAA) on the expression of VEGF and IL-10 genes in chronic hepatitis C virus-infected Egyptian genotype-4a patients. Twenty-five HCV subjects where evaluated for IL-10 and VEGF gene expression before and after treatment with DAA. Results IL-10 expression was downregulated in 92% of the cases. VEGF expression was heterogeneous showing spreading of values along a wide range with 64% of the cases being downregulated. Conclusion DAAs do not completely reverse the immunological imprints established upon chronic HCV infection.

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