Shift in the Balance between Circulating Thrombospondin-1 and Vascular Endothelial Growth Factor in Cancer Patients: Relationship to Platelet α-Granule Content and Primary Activation

2004 ◽  
Vol 19 (3) ◽  
pp. 221-228 ◽  
Author(s):  
F.J. Gonzalez ◽  
A. Rueda ◽  
I. Sevilla ◽  
L. Alonso ◽  
V. Villarreal ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Cancer Patients ◽  
Platelet Activation ◽  
Healthy Subjects ◽  
Plasma Concentrations ◽  
Angiogenesis Inhibitor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Primary Activation

Tumoral angiogenesis is regulated by the balance between factors that activate and inhibit angiogenesis. Elevated levels of activators have been associated with a poor prognosis in cancer patients, but little is known about the net balance between circulating activators and inhibitors in these patients. This study was designed to determine whether the balance between circulating concentrations of the angiogenesis inhibitor TSP-1 and the activator VEGF differs from that in healthy persons, and to shed light on the possible role of platelets in this balance. Twenty-five cancer patients and 18 healthy subjects were included. Serum and plasma concentrations of VEGF, TSP-1 and PF4 were measured by ELISA. Our results showed that in healthy subjects the balance between the TSP-1 and VEGF concentrations in serum and in serum minus plasma was twice to three times as high as in cancer patients (p<0.05). The theoretical TSP-1 content per platelet was greater in healthy subjects than in patients (94 vs. 53.6 ng/mL, p<0.05), and platelet activation (determined indirectly as the plasma concentration of PF4) was greater in cancer patients (129 vs. 48 IU/mL, p<0.01). Platelet activation correlated significantly with serum concentration of TSP-1 (r=0.470, p=0.018) and showed a tendency toward correlation with plasma concentration of TSP-1 (r=0.382, p=0.059). Our findings show that the circulating TSP-1/VEGF balance is diminished in cancer patients. Platelet activation may play an important role in this decrease and may ultimately lead to increased angiogenic activity in these patients.

Abstract 1298: Adipocytes Produce The Angiogenesis Inhibitor, Soluble Fms-like Tyrosine Kinase (sflt-1)

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Florian Herse ◽  
Lydia Hering ◽  
Juergen Janke ◽  
Kerstin Gorzcelniak ◽  
Stefan Engeli ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Angiogenesis Inhibitor ◽  
Vascular Endothelial ◽  
Fat Cell ◽  
Tnf Α ◽  
17Β Estradiol ◽  
Low Bmi ◽  
Endothelial Growth Factor ◽  
Necrosis Factor

Vascular endothelial growth factor (VEGF) exerts its effects via receptors, including Flt-1. sFLT-1 is a soluble splice variant that binds VEGF locally so that the molecule cannot signal; sFLT-1 is implicated in preeclampsia, a condition associated with obesity. Adipose tissue has a dense vascular network regulated in part by LYVE-1-expressing macrophages and VEGF. The role of sFLT-1 in adipose tissue angiogenesis has not been investigated. We used RT-PCR and found that sFlt-1 was 2.6-fold upregulated in adipose tissue from preeclamptic women, 2.5-fold in decidua, and 6.9-fold in placenta. Circulating sFlt-1 was 2.4-fold elevated (all compared to pregnant nonpreeclamptic controls; p<0.05). We next cultured human preadi-pocytes and adipocytes to examine sFlt-1 and VEGF. sFlt-1 expression increased 9-fold as preadipocytes matured to adipocytes. Adipocytes actively secreted sFlt-1 into the supernatant. Hypoxia (O2 tension reduced to 3%) did not alter sFlt-1 mRNA, while VEGF expression increased 4-fold. Tumor necrosis factor (TNF)- α (100 ng/ml, 48 h) induced VEGF 2-fold, but reduced sFlt-1 production 4-fold. Angiotensin II, insulin, hydrocortisone, pioglitazone, and 17β-estradiol all had no influcence on adipocyte sFlt-1 expression. In fat tissue biopsies from 69 postmenopausal women, sFlt-1 correlated inversely with BMI (r=-0.36, p=0.002), but directly with adiponectin expression (r=0.33, p=0.01). No significant correlation was found to blood pressure, insulin, or microalbuminuria. Our study shows that sFlt-1 is elevated in the circulation, placenta, and is upregulated in adipose tissue from preeclamptic women. sFlt-1 is expressed and secreted by adipocytes. sFlt-1 is elevated during fat cell differentiation and downregulated by TNF-α. In healthy postmeonopausal women, adipose tissue sFlt-1 correlates with low BMI and high adiponectin expression. We speculate that secreted sFlt-1 from adipocytes may contribute to the vascular damage during preeclampsia. Furthermore, sFlt-1 may play a regulatory role in adipose tissue under other circumstances, perhaps as an angiogenesis regulating factor.

scholarly journals The Role of Vascular Endothelial Growth Factorin Thrombocytosis in Colorectal Cancer Patients

2018 ◽  
Vol 2 (2) ◽  
pp. 1-7
Author(s):  
Subandrate Subandrate ◽  
Dwi Indira Setyorini ◽  
Mediarty Mediarty ◽  
Irsan Saleh
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Serum Levels ◽  
Vascular Endothelial ◽  
Research Subjects ◽  
Elisa Technique ◽  
Average Serum ◽  
Colorectal Cancer Patients ◽  
Endothelial Growth Factor

Backgorund: Colorectal cancer was included in a group of cancer with various complications. One complication that was often a cause of morbidity and mortality was thrombocytosis. In colorectal cancer, the incidence of thrombocytosis associated with the formation of blood vessels around the tumor or angiogenesis. Factors that played an important role in angiogenesis was vascular endothelial growth factor (VEGF). Methods: This study was an observational analytic research in colorectal cancer patients to determine the correlation levels of platelets and serum VEGF levels. A total of 33 patients with colorectal cancer at the Palembang Mohammad Hoesin Hospital be research subjects to examine the levels of platelets and levels of VEGF. The level of serum VEGF was performed using ELISA technique from SIGMA®. Results: The average level of the patient's platelets was281,090.9±105,860.8/mm3.  In this study, two patients (6.06%) have thrombocytosis.The average serum levels of VEGF research subjects were 221.2 ± 152.8 pg/mL.Correlation test of levels of serum VEGF and platelets levels showed the value of p=0.040 (p> 0.05) and r = 0468. Conclusions: Thus, it can be concluded that in this research serum VEGF levels are almost always causes an increase in platelet levels in patients with colorectal cancer.

scholarly journals The contribution of dietary and plasma folate and cobalamin to levels of angiopoietin-1, angiopoietin-2 and Tie-2 receptors depend on vascular endothelial growth factor status of primary breast cancer patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Saeed Pirouzpanah ◽  
Parisa Varshosaz ◽  
Ashraf Fakhrjou ◽  
Vahid Montazeri
Keyword(s):  
Breast Cancer ◽  
Folic Acid ◽  
Cancer Patients ◽  
Structural Equation ◽  
Equation Modeling ◽  
Vascular Endothelial ◽  
Breast Cancer Patients ◽  
Dietary Folate ◽  
Endothelial Growth Factor

Abstract The aim of this study was to determine the association of dietary folate and cobalamin with plasma levels of Angiopoietins (ANG), vascular endothelial growth factor-C (VEGF-C) and tyrosine kinase receptor-2 (Tie-2) of primary breast cancer patients. Women (n = 177), aged 30 to 75 years diagnosed with breast cancer were recruited from an ongoing case series study. Dietary intake of nutrients was estimated by using a validated food frequency questionnaire. Enzyme-linked immunosorbent assay was applied to measure biomarkers. MCF-7 cell cultures were supplemented with folic acid (0–40 μM) for 24 h to measure cell viability and fold change of expression by the real-time reverse transcriptase-polymerase chain reaction. Structural equation modeling was applied to analyze the structural relationships between the measured variables of nutrients and Angiopoietins. Dietary intake of folate and cobalamin showed a significant inverse correlation with plasma ANG-1 and ANG-2 (P < 0.05), particularly in subjects with estrogen-receptor positive tumors or low plasma VEGF-C. Plasma folate was positively associated with the ratio of ANG-1/ANG-2 (P < 0.05). Residual intake levels of total cobalamin were inversely associated with plasma ANG-1 when plasma stratum of VEGF-C was high (P < 0.05). Structural equation modeling identified a significant inverse contribution of folate profiles on the latent variable of Angiopoietins (coefficient β = −0.99, P < 0.05). Folic acid treatment resulted in dose-dependent down-regulations on ANGPT1 and ANGPT1/ANGPT2 ratio but VEGF and ANGPT2/VEGF were upregulated at folic acid >20 μM. Studying the contributing role of dietary folate to pro-angiogenic biomarkers in breast cancer patients can infer the preventive role of folate in the ANGs/VEGF-C-dependent cascade of tumor metastasis. By contrast, high concentrations of folic acid in vitro supported VEGF-C-dependent ANGPT2 overexpression might potentiate micro-lymphatic vessel development to support malignant cell dissemination.

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