Leukocytes and platelets of patients with cancer contain high levels of vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-sp ecific mitogen and permeability factor, Malignant human tumors have been sh own to produce VEGF, Elevated levels of VEGF have been detected in sera of canter patients, but its origin is unsettled. We analyzed VEGF concentratio ns in serum, plasma, whole blood, and peripheral blood mononuclear cells (P BMNCs) and platelets in 56 cancer patients and 52 healthy controls using EL ISA. The VEGF concentrations in the lysed whole blood samples [blood VEGF ( B-VEGF)] were higher in cancer patients than in healthy controls (median, 4 64 versus 298 pg/ml; P < 0.0001). The highest B-VEGF values were found in d isseminated cancer. In cancer patients, a high B-VEGF concentration was ass ociated with a high peripheral blood leukocyte count (P = 0.0012) and plate let count (P = 0.09), In healthy individuals, a high B-VEGF was associated with a high leukocyte count (P = 0.0001) but not with the platelet count (P > 0.1). The cancer patients regularly had higher B-VEGF concentrations tha n healthy individuals with comparable leukocyte or platelet counts. The VEG F content of isolated PBMNCs and platelets was severalfold higher in cancer patients than in healthy controls (median, 10.6 versus 0.9 pg per 10(6) PB MNCs, and median, 1.6 versus 0.5 pg per ;10(6) platelets; P < 0.0001 and P = 0.0008, respectively). Serum VEGF and B-VEGF correlated strongly (P < 0.0 001). Very little or no VEGF was found in the plasma. The results indicate that VEGF in the bloodstream is transported by blood cells, including leuko cytes and platelets. The blood cells of cancer patients contain greatly ele vated amounts of this major angiogenic growth factor, and this reservoir of VEGF may have a role in tumor angiogenesis and metastasis formation. VEGF in serum samples originates from blood cells, and the use of VEGF of whole blood or of isolated blood cells may improve the clinical value of VEGF mea surements.