Vascular endothelial growth factor levels and induction of permeability in malignant pleural effusions

Clin Cancer Res. 1999 Nov;5(11):3364-8.

Abstract

Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis and vascular permeability. We hypothesized that malignant pleural effusions may contain high levels of VEGF protein as well as other cytokines implicated in these processes. Pleural effusions cytologically proven to be malignant were collected from 39 patients with various types of cancer, and VEGF, interleukin-8, and angiogenin levels in the effusions were determined by immunoassay. Negative controls were nonmalignant ascites and serum samples from healthy individuals. VEGF levels were significantly higher than those of control samples in pleural effusions secondary to breast, mesothelioma, and non-small cell lung cancer and when all malignant pleural effusion samples were pooled. Neither interleukin-8 nor angiogenin levels were elevated in malignant pleural effusions relative to the control samples. Vascular permeability, which was measured by using the Miles assay in nude mice, was increased proportionately with VEGF levels in the malignant pleural effusions; 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inducing Agents / analysis
  • Angiogenesis Inducing Agents / metabolism
  • Animals
  • Breast Neoplasms / pathology
  • Capillary Permeability / drug effects
  • Capillary Permeability / physiology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Endothelial Growth Factors / analysis
  • Endothelial Growth Factors / metabolism*
  • Endothelial Growth Factors / pharmacology
  • Female
  • Humans
  • Interleukin-8 / analysis
  • Interleukin-8 / metabolism*
  • Lung Neoplasms / pathology
  • Lymphokines / analysis
  • Lymphokines / metabolism*
  • Lymphokines / pharmacology
  • Lymphoma / pathology
  • Male
  • Mesothelioma / pathology
  • Mice
  • Mice, Nude
  • Pleural Effusion, Malignant / chemistry
  • Pleural Effusion, Malignant / metabolism*
  • Pleural Effusion, Malignant / physiopathology*
  • Proteins / analysis
  • Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptors, Growth Factor / physiology
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Proteins / pharmacology
  • Ribonuclease, Pancreatic*
  • Sarcoma / pathology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Angiogenesis Inducing Agents
  • Endothelial Growth Factors
  • Interleukin-8
  • Lymphokines
  • Proteins
  • Receptors, Growth Factor
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor
  • angiogenin
  • Ribonuclease, Pancreatic