This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Verheul, H. M. W. Articles by Pinedo, H. M. Search for Related Content PubMed PubMed Citation Articles by Verheul, H. M. W. Articles by Pinedo, H. M.

Platelet and Coagulation Activation with Vascular Endothelial Growth Factor Generation in Soft Tissue Sarcomas

Departments of Medical Oncology [H. M. W. V., K. H., H. J. B., H. M. P.] and Pathology [P. v. d. V.], University Hospital "Vrije Universiteit," 1007 MB Amsterdam, the Netherlands; Weston Centre for Experimental Research, Thrombosis Research Institute, London SW3 6LR, United Kingdom [F. L.]; and Department of Surgery, Imperial College School of Medicine, Hammersmith Hospital, London WI2 0NV, United Kingdom [A. K. K.]

Angiogenesis and activated blood coagulation are involved in tumor growth and metastasis. Although some have suggested that activation of coagulation in tumors is not linked to activation of platelets, no data exist to either support or refute this concept. However, platelet turnover in cancer patients is often increased, and platelets are carriers of angiogenic growth factors. We hypothesized that platelets are involved in tumor-associated angiogenesis. To obtain evidence supporting this hypothesis, we have studied whether the angiogenic and coagulation pathways and platelets are concomitantly activated in cancer patients with soft tissue sarcomas (STSs) using a novel method to detect activated platelets in tumor specimens. Twelve patients with STS were selected on the basis of having intratumoral accumulation of fluid, which was aspirated. These accumulations demonstrated very high concentrations of vascular endothelial growth factor and coagulation factors (including thrombin-antithrombin-complex). Tumor specimens showed dense vascularization with intense vascular endothelial growth factor expression and the presence of activated platelets. Taken together, these results support the concept that angiogenesis, blood coagulation, and platelets are concomitantly activated in STS and support the hypothesis that platelets contribute to tumor-induced angiogenesis.

This article has been cited by other articles:

				H. M.W. Verheul, M. P.J. Lolkema, D. Z. Qian, Y. H.A. Hilkes, E. Liapi, J.-W. N. Akkerman, R. Pili, and E. E. Voest Platelets Take Up the Monoclonal Antibody Bevacizumab Clin. Cancer Res., September 15, 2007; 13(18): 5341 - 5347. [Abstract] [Full Text] [PDF]

				H. M.W. Verheul, H. Hammers, K. van Erp, Y. Wei, T. Sanni, B. Salumbides, D. Z. Qian, G. D. Yancopoulos, and R. Pili Vascular Endothelial Growth Factor Trap Blocks Tumor Growth, Metastasis Formation, and Vascular Leakage in an Orthotopic Murine Renal Cell Cancer Model Clin. Cancer Res., July 15, 2007; 13(14): 4201 - 4208. [Abstract] [Full Text] [PDF]

				H. G. KOPP and S. RAFII Thrombopoietic Cells and the Bone Marrow Vascular Niche Ann. N.Y. Acad. Sci., June 1, 2007; 1106(1): 175 - 179. [Abstract] [Full Text] [PDF]

				A. Kunita, T. G. Kashima, Y. Morishita, M. Fukayama, Y. Kato, T. Tsuruo, and N. Fujita The Platelet Aggregation-Inducing Factor Aggrus/Podoplanin Promotes Pulmonary Metastasis Am. J. Pathol., April 1, 2007; 170(4): 1337 - 1347. [Abstract] [Full Text] [PDF]

				A H G Hansma, Y van Hensbergen, B C Kuenen, P J van Diest, R Hanemaaijer, S Meijer, H M Pinedo, and K Hoekman A patient with a VEGF and endostatin producing gastrointestinal autonomic nerve tumour J. Clin. Pathol., May 1, 2004; 57(5): 536 - 538. [Abstract] [Full Text] [PDF]

				M. E. Daly, A. Makris, M. Reed, and C. E. Lewis Hemostatic Regulators of Tumor Angiogenesis: A Source of Antiangiogenic Agents for Cancer Treatment? J Natl Cancer Inst, November 19, 2003; 95(22): 1660 - 1673. [Abstract] [Full Text] [PDF]

				P. Jurasz, D. Alonso, S. Castro-Blanco, F. Murad, and M. W. Radomski Generation and role of angiostatin in human platelets Blood, November 1, 2003; 102(9): 3217 - 3223. [Abstract] [Full Text] [PDF]

				H. M. W. Verheul and H. M. Pinedo The Importance of Platelet Counts and Their Contents in Cancer Clin. Cancer Res., August 1, 2003; 9(9): 3219 - 3221. [Full Text] [PDF]

				B.C. Kuenen, M. Levi, J.C.M. Meijers, V.W.M. van Hinsbergh, J. Berkhof, A.K. Kakkar, K. Hoekman, and H.M. Pinedo Potential Role of Platelets in Endothelial Damage Observed During Treatment With Cisplatin, Gemcitabine, and the Angiogenesis Inhibitor SU5416 J. Clin. Oncol., June 1, 2003; 21(11): 2192 - 2198. [Abstract] [Full Text] [PDF]

				B. C. Kuenen, J. Tabernero, J. Baselga, F. Cavalli, E. Pfanner, P. F. Conte, S. Seeber, S. Madhusudan, G. Deplanque, H. Huisman, et al. Efficacy and Toxicity of the Angiogenesis Inhibitor SU5416 As a Single Agent in Patients with Advanced Renal Cell Carcinoma, Melanoma, and Soft Tissue Sarcoma Clin. Cancer Res., May 1, 2003; 9(5): 1648 - 1655. [Abstract] [Full Text] [PDF]

				P. C. Manegold, J. Hutter, S. A. Pahernik, K. Messmer, and M. Dellian Platelet-endothelial interaction in tumor angiogenesis and microcirculation Blood, March 1, 2003; 101(5): 1970 - 1976. [Abstract] [Full Text] [PDF]

				Y. van Hensbergen, H. J. Broxterman, R. Hanemaaijer, A. S. Jorna, N. A. van Lent, H. M. W. Verheul, H. M. Pinedo, and K. Hoekman Soluble Aminopeptidase N/CD13 in Malignant and Nonmalignant Effusions and Intratumoral Fluid Clin. Cancer Res., December 1, 2002; 8(12): 3747 - 3754. [Abstract] [Full Text] [PDF]

				P. A. Burke, S. J. DeNardo, L. A. Miers, K. R. Lamborn, S. Matzku, and G. L. DeNardo Cilengitide Targeting of {alpha}v{beta}3 Integrin Receptor Synergizes with Radioimmunotherapy to Increase Efficacy and Apoptosis in Breast Cancer Xenografts Cancer Res., August 1, 2002; 62(15): 4263 - 4272. [Abstract] [Full Text] [PDF]

				M. C. A. Duyndam, M. C. G. W. Hilhorst, H. M. M. Schluper, H. M. W. Verheul, P. J. van Diest, G. Kraal, H. M. Pinedo, and E. Boven Vascular Endothelial Growth Factor-165 Overexpression Stimulates Angiogenesis and Induces Cyst Formation and Macrophage Infiltration in Human Ovarian Cancer Xenografts Am. J. Pathol., February 1, 2002; 160(2): 537 - 548. [Abstract] [Full Text] [PDF]

				R. T.-P. Poon, S.-T. Fan, and J. Wong Clinical Implications of Circulating Angiogenic Factors in Cancer Patients J. Clin. Oncol., February 15, 2001; 19(4): 1207 - 1225. [Abstract] [Full Text] [PDF]

				M. George, S. Eccles, G. Box, M. Tutton, M. Abulafi, and I. Swift Reply Clin. Cancer Res., February 1, 2001; 7(2): 444 - 444. [Full Text]

				P. Jurasz, G. Sawicki, M. Duszyk, J. Sawicka, C. Miranda, I. Mayers, and M. W. Radomski Matrix Metalloproteinase 2 in Tumor Cell-induced Platelet Aggregation: Regulation by Nitric Oxide Cancer Res., January 1, 2001; 61(1): 376 - 382. [Abstract] [Full Text]

				H. M. W. Verheul, A. S. Jorna, K. Hoekman, H. J. Broxterman, M. F. B. G. Gebbink, and H. M. Pinedo Vascular endothelial growth factor-stimulated endothelial cells promote adhesion and activation of platelets Blood, December 15, 2000; 96(13): 4216 - 4221. [Abstract] [Full Text] [PDF]

				H.M.W. Verheul, K. Hoekman, A.S. Jorna, E.F. Smit, and H.M. Pinedo Targeting Vascular Endothelial Growth Factor Blockade: Ascites and Pleural Effusion Formation Oncologist, April 1, 2000; 5(90001): 45 - 50. [Abstract] [Full Text]