Thrombocytes Are the Major Source for Soluble Vascular Endothelial Growth Factor in Peripheral Blood

Abstract

Serum levels of vascular endothelial growth factor (VEGF-S) have been reported to correlate with tumor stage and prognosis in various human malignancies. The source of soluble VEGF in peripheral blood remains obscure. We therefore measured the concentration of immunoreactive VEGF in 241 serum samples and 61 plasma samples (VEGF-P) from 20 subjects undergoing myeloablative chemotherapy and from 3 normal platelet donors. A significant correlation between the peripheral blood platelet count (PC) and VEGF-S (r = 0.86) but not VEGF-P was found. VEGF-S levels were 58.43 ± 42.50 pg/ml (mean ± SD) in patients with a PC < 50 × 10⁹/l, 203.29 ± 176.56 pg/ml for a PC of 50–150 × 10⁹/l, and 457.42 ± 475.41 pg/ml for a PC > 150 × 10⁹/l. Interestingly, VEGF-P levels were substantially lower than the corresponding VEGF-S values, namely below the detection limit in most cases. Supernatants from platelet-rich plasma contained no VEGF, but after in vitro lysis of the platelets very high VEGF levels were found. The VEGF content per 10⁹ platelets was calculated at 2.51 ± 2.39 pg and was dependent on the mean platelet volume. In summary, VEGF release from platelets during blood clotting was found to be the main source of VEGF in serum samples. Cancer patients in clinical remission have negligible amounts of soluble VEGF in peripheral blood, and myeloablative chemotherapy causes a significant drop in VEGF-S levels corresponding to the decrease in PC. Thus, studies addressing the diagnostic and prognostic value of VEGF-S in cancer patients must be interpreted with caution. Our data provide the basis for predicting VEGF-S in relation to PC in vivo, and for reevaluating former studies of VEGF-S in patients with malignant or nonmalignant disease.

Increased bone marrow microvascular density in haematological malignancies is associated with differential regulation of angiogenic factors

“…27 We measured VEGF levels in plasma as 80-90% of the VEGF levels measured in serum originate from ex vivo activated platelets. 28 Increased levels of circulating VEGF have been demonstrated previously in patients with the haematological malignancies in this study. [29][30][31][32] Higher pretreatment plasma levels of VEGF in patients who did not obtain CR has been demonstrated previously in AML 29 and NHL.…”

Serum levels of angiogenin, basic fibroblast growth factor and endostatin in patients receiving intensive chemotherapy for acute myelogenous leukemia

“…Approximately 80 -90% of serum VEGF levels are derived from ex vivo activated platelets, and serum VEGF levels therefore correlate with the platelet count in peripheral blood. 53 Peripheral blood platelet counts show a wide variation in acute leukemia patients, and platelet counts are usually reduced from normal (140 -400 ϫ All these patients had received previous intensive chemotherapy, but no chemotherapy had been administered during the last 25 days. At the time of testing, the patients had achieved initial disease control with complete hematologic remission characterized by (i) a normocellular bone marrow with a normal number of immature blast cells (corresponding to Ͻ5% of the nucleated cells); and (ii) effective hematopoiesis with normal leukocyte counts and platelet counts Ͼ 100 ϫ 10 9 /1 in the peripheral blood.…”

Surgery for gastric cancer increases plasma levels of vascular endothelial growth factor and von Willebrand factor

“…At metastatic sites, it has been suggested that platelets aggregate due to factors released from metastatic cells and direct contact with metastatic cells, resulting in microthrombosis, tumor adhesion, and growth. In this step, VEGF could be released from activated platelets, and this released VEGF could induce the neovascular formation for tumor cell invasion and growth [13,25].…”