Markedly elevated levels of vascular endothelial growth factor in malignant ascites

Background: Vascular endothelial growth factor (VEGF) is a potent angiogeni c factor that also has the ability to increase vascular permeability. Malig nant ascites has significant morbidity, but the mechanism of its developmen t is unknown. Because of the permeability-inducing properties of VEGF, we h ypothesized that malignant ascites formation is associated with high levels of VEGF. The purpose of our study was to determine the role of VEGF in mal ignant ascites formation. Methods: Ascites from 25 patients with gastric (n = 6), colon (n = 7), or o varian (n = 12) cancers was collected by paracentesis or surgery. VEGF prot ein levels were determined by enzyme-linked immunosorbent assay. The effect of ascites on endothelial cell permeability was assessed by evaluating pro pidium iodide uptake by human umbilical vein endothelial cells (HUVECs) exp osed 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 c ompared with levels in nonmalignant cirrhotic ascites (controls). VEGF prot ein levels in ovarian, gastric, and colon cancer ascites were found to be i ncreased 45, 23, and 12 times, respectively, compared with levels in cirrho tic ascites. Malignant ascites from patients with colon and gastric cancer caused an increase in permeability in HUVECs in all cases. Neutralizing VEG F 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 endothe lial cell permeability.