Thrombocytes are the major source for soluble vascular endothelial growth factor in peripheral blood

Serum levels of vascular endothelial growth factor (VEGF-S) have been repor ted to correlate with tumor stage and prognosis in various human malignanci es. The source of soluble VEGF in peripheral blood remains obscure. We ther efore measured the concentration of immunoreactive VEGF in 241 serum sample s and 61 plasma samples (VEGF-P) from 20 subjects undergoing myeloablative chemotherapy and from 3 normal platelet donors. A significant correlation b etween the peripheral blood platelet count (PC) and VEGF-S (r = 0.86) but n ot VEGF-P was found. VEGF-S levels were 58.43 +/- 42.50 pg/ml (mean +/- SD) in patients with a PC < 50 x 10(9)/l, 203.29 +/- 176.56 pg/ml for a PC of 50-150 x 10(9)/l, and 457.42 +/- 475.41 pg/ml for a PC > 150 x 10(9)/l. Int erestingly, VEGF-P levels were substantially lower than the corresponding V EGF-S values, namely below the detection limit in most cases. Supernatants from platelet-rich plasma contained no VEGF, but after in vitro lysis of th e platelets very high VEGF levels were found. The VEGF content per 10(9) pl atelets was calculated at 2.51 +/- 2.39 pg and was dependent on the mean pl atelet volume. In summary, VEGF release from platelets during blood clottin g was found to be the main source of VEGF in serum samples. Cancer patients in clinical remission have negligible amounts of soluble VEGF in periphera l blood, and myeloablative chemotherapy causes a significant drop in VEGF-S levels corresponding to the decrease in PC. Thus, studies addressing the d iagnostic and prognostic value of VEGF-S in cancer patients must be interpr eted with caution. Our data provide the basis for predicting VEGF-S in rela tion to PC in vivo, and for reevaluating former studies of VEGF-S in patien ts with malignant or nonmalignant disease. Copyright (C) 2000 S. Karger AG, Basel