Correspondence re: M. L. George et al., Correlation of Plasma and Serum Vascular Endothelial Growth Factor Levels with Platelet Count in Colorectal Cancer: Clinical Evidence of Platelet Scavenging? Clin. Cancer Res., 6: 3147−3152, 2000. Eberhard Gunsilius, Joerg Tschmelitsch and Andreas. L. Petzer Clin Cancer Res 2001;7:443.
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Vol. 7, 443, February 2001
Clinical Cancer Research 443
Letters to the Editor Correspondence re: H. L. George et al., Correlation of Plasma and Serum Vascular Endothelial Growth Factor Levels with Platelet Count in Colorectal Cancer: Clinical Evidence of Platelet Scavenging? Clin. Cancer Res., 6: 3147–3152, 2000. We appreciate the findings of George et al. (1), which are the offspring of a very well conducted study. We totally agree that VEGF1 serum levels, corrected for the blood platelet count, are the best way to assess VEGF circulating in blood (2). Their hypothesis that platelets are scavenging VEGF circulating in the bloodstream, resulting in a counterbalance of VEGFPLT as a consequence of loss of tumor-derived VEGF after tumor removal and VEGF-release induced by surgical trauma, is intriguing. However, the amount of VEGF circulating in the blood of patients with cancer is likely to be derived from various sources, as depicted in the Fig. 1. We found significantly higher VEGF levels in plasma samples obtained during surgery from tumor-draining mesenteric veins compared with peripheral blood, especially in histologically undifferentiated tumors that are known to be highly angiogenic (3). This may be explained by the local release of VEGF from tumor cells into the bloodstream (Fig. 1A) and/or from thrombocytes activated at the tumor-vessel endothelium. In patients with cancer, platelet activation and consumption is a well-known phenomenon. Activated platelets release VEGF in vivo, which may contribute to the elevated plasma levels observed in these patients (Fig. 1B). Moreover, platelet consumption causes increased levels of thrombopoietin, which stimulates megakaryopoiesis and platelet production in the bone marrow. Newly produced platelets are larger in size than those produced during steady state thrombopoiesis, resulting in elevated VEGFPLT (Fig. 1C; Ref. 4). The finding that maximal VEGFPLT corrected for VEGF plasma levels occurs in patients with advanced disease fits well into this assumption. Finally, host immune cells as macrophages (M⌽) that infiltrate tumor tissues can be an additional source of VEGF (Fig. 1, D; Ref. 5).
Eberhard Gunsilius Joerg Tschmelitsch Andreas. L. Petzer Guenther Gastl Division of Hematology and Oncology, and Department of Surgery University Hospital Anichstrasse 35 6020 Innsbruck Austria
Fig. 1 VEGF circulating in the blood of patients with cancer.
References 1. George, M. L., Eccles, S. A., Tutton, M. G., Abulafi, A. M., and Swift, R. I. Correlation of plasma and serum vascular endothelial growth factor levels with platelet count in colorectal cancer: clinical evidence of platelet scavenging? Clin. Cancer Res., 6: 3147–3152, 2000. 2. Gunsilius, E., Petzer, A., Stockhammer, G., Nussbaumer, W., Schumacher, P., Clausen, J., and Gastl, G. Thrombocytes are the major source for soluble vascular endothelial growth factor in peripheral blood. Oncology (Basel), 58: 169 –174, 2000. 3. Tschmelitsch, J., Eberwein, M., Schwelberger, H., Gastl, G., and Gunsilius, E. Vascular endothelial growth factor levels in mesenteric and peripheral blood from patients with colorectal cancer: correlation with tumor stage and histological grading. Acta Med. Austriaca, 26: 20, 1999. 4. Gunsilius, E., and Gastl, G. Platelets and VEGF blood levels in cancer patients. Br. J. Cancer, 81: 185–186, 1999. 5. Leek, R. D., Hunt, N. C., Landers, R. J., Lewis, C. E., Royds, J. A., and Harris, A. L. Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer. J. Pathol., 190: 430 – 436, 2000.
1 The abbreviations used are: VEGF, vascular endothelial growth factor; VEGFPLT, platelet-derived VEGF.
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1102 Vol. 7, 1103, April 2001
Clinical Cancer Research
Corrections In the Letter by E. Gunsilius et al, which appeared in the February, 2001 issue of Clinical Cancer Research (pg. 443) the title should read “Correspondence re: M.L. George et al.,” instead of “Correspondence re: H.L. George et al.” In the article by L.M. Krug et al, which appeared in the September, 2000 issue of Clinical Cancer Research (pp. 3493–3498), the author “Stefan C. Grant” was omitted: the complete author list should read: “Krug, L.M., Ng, K.K., Kris, M.G., Miller, V.A., Tong, W., Heelan, R.T., Leon, L., Leung, D., Kelly, J., Grant, S.C., and Sirotnak, F.M.”.
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