Vascular endothelial growth factor levels and induction of permeability inmalignant pleural effusions

Vascular endothelial growth factor (VEGF) is an important mediator of angio genesis and vascular permeability, We hypothesized that malignant pleural e ffusions may contain high levels of VEGF protein as well as other cytokines implicated in these processes. Pleural effusions cytologically proven to b e malignant were collected from 39 patients with various types of cancer, a nd VEGF, interleukin-8, and angiogenin levels in the effusions were determi ned by immunoassay. Negative controls were nonmalignant ascites and serum s amples from healthy individuals. VEGF levels were significantly higher than those of control samples in pleural effusions secondary to breast, mesothe lioma, and non-small cell lung cancer and when all malignant pleural effusi on samples were pooled. Neither interleukin-8 nor angiogenin levels were el evated in malignant pleural effusions relative to the control samples. Vasc ular permeability, which was measured by using the Miles assay in nude mice , was increased proportionately with VEGF levels in the malignant pleural e ffusions; this increase in permeability induced by injection of recombinant VEGF or the malignant effusions was reduced by pretreating the mice with a VEGF receptor antibody.