Circulating endothelial cells in cancer patients do not express tissue factor.
Numbers of circulating endothelial cells (CECs) are increased in cancer patients with progressive disease. Also, cancer patients have an increased risk for thrombotic events, being negatively associated with prognosis. Tissue factor (TF), the physiological initiator of coagulation, is present on the surface of many extravascular cells. In 34 samples from cancer patients and in seven from volunteers, CECs were quantified (with endothelium-specific anti-CD146 beads), and TF-activity assessed with a chromogenic assay. All samples displayed very limited TF-activity (patients: 1.6+/-3.1 microU; volunteers: 0.94+/-1.7 microU FXa/100 CECs, P = 0.30 by Mann-Whitney test). After in vitro TNFalpha-stimulation, CECs from both cancer patients and volunteers showed substantially increased TF-activity (endogenous activity: 17.3+/-6.4 microU; after TNFalpha-stimulation: 73.8+/-34.3 microU FXa; P = 0.028, Wilcoxon signed ranks test), reflecting the potential of CECs to generate biologically active TF. As the chromogenic assay determines a mean cellular TF-activity, we also analyzed immunohistochemical TF-antigen expression on CEC subsets. TF-antigen expression was undetectable. CECs isolated from cancer patients do not express TF. CECs can generate functional TF after stimulation and may therefore play a role in (intratumoral) coagulation induction and tumor angiogenesis.
Laboratory of Experimental Oncology, Department of Medical Oncology, HP F02.126, University Medical Center Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA, The Netherlands.
Laurens V
LV
Beerepoot
Niven
N
Mehra
Frank
F
Linschoten
Anita S
AS
Jorna
Ton
T
Lisman
Henk M W
HM
Verheul
Emile E
EE
Voest
D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009369:Neoplasms / Q000150:complications*; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012307:Risk Factors; D013925:Thromboplastin / Q000032:analysis* / Q000494:pharmacology*; D013927:Thrombosis / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014408:Biomarkers, Tumor; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin