Platelet and coagulation activation with vascular endothelial growth factor generation in soft tissue sarcomas.
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.
Verheul
H M
HM
Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Hoekman
K
K
Lupu
F
F
Broxterman
H J
HJ
van der Valk
P
P
Kakkar
A K
AK
Pinedo
H M
HM
D000990:Antithrombin III / Q000032:analysis; D001792:Blood Platelets / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000032:analysis*; D018219:Histiocytoma, Benign Fibrous / Q000098:blood supply / Q000473:pathology; D006801:Humans; D007890:Leiomyosarcoma / Q000098:blood supply / Q000473:pathology; D008222:Lymphokines / Q000032:analysis*; D009389:Neovascularization, Pathologic; D010447:Peptide Hydrolases / Q000032:analysis; D015539:Platelet Activation; D012509:Sarcoma / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology*; D018180:Thrombomodulin / Q000032:analysis; D013925:Thromboplastin / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D018180:Thrombomodulin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases