Markedly Elevated Levels of Vascular Endothelial Growth Factor in Malignant Ascites

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Abstract
Background: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also has the ability to increase vascular permeability. Malignant ascites has significant morbidity, but the mechanism of its development is unknown. Because of the permeability-inducing properties of VEGF, we hypothesized that malignant ascites formation is associated with high levels of VEGF. The purpose of our study was to determine the role of VEGF in malignant ascites formation. Methods: Ascites from 25 patients with gastric (n = 6), colon (n = 7), or ovarian (n = 12) cancers was collected by paracentesis or surgery. VEGF protein levels were determined by enzyme-linked immunosorbent assay. The effect of ascites on endothelial cell permeability was assessed by evaluating propidium iodide uptake by human umbilical vein endothelial cells (HUVECs) exposed to ascites. Neutralizing antibodies to VEGF added to ascites were used to determine the causal effect of VEGF in permeability induction. Results: VEGF protein levels were markedly increased in malignant ascites compared with levels in nonmalignant cirrhotic ascites (controls). VEGF protein levels in ovarian, gastric, and colon cancer ascites were found to be increased 45, 23, and 12 times, respectively, compared with levels in cirrhotic ascites. Malignant ascites from patients with colon and gastric cancer caused an increase in permeability in HUVECs in all cases. Neutralizing VEGF activity in colon cancer ascites decreased in-vitro HUVEC permeability in three of four cases. Conclusions: VEGF protein levels are markedly elevated in malignant ascites. VEGF may play a role in malignant ascites formation by increasing endothelial cell permeability.