Hemostasis and cancer

Tumor cells induce the expression of tissue factor-like procoagulant activity on endothelial cells

Anna Maiolo, Aldo Tua, Guido Grignani

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background and Objectives. Clotting activation and thromboembolic manifestations are common features in patients with cancer. The two-way interaction between tumor cells and host cells is of crucial importance in this context. In the present study we investigated the effect of tumor cell-endothelial cell co-culture on the expression of procoagulant activity in the mixed cell populations. Design and Methods. Human tumor cell lines (HL60 promyelocytic leukemia and HeLa uterine cervical cancer) and human umbilical vein endothelial cells (HUVEC) were cultured in vitro according to standard procedures. Procoagulant activity was studied in a coagulometer and was found to be tissue factor-like. A calibration curve was obtained with decreasing concentrations of rabbit brain thromboplastin (RBT) and the procoagulant activity of both tumor cells and HUVEC was expressed as RBT U/105 cells. Results. Before incubation procoagulant activity (mean ± SE) was found to be 0.18 ± 0.04 U in HUVEC, 9.8 ± 1.9 U in HL60 cells, 11.9 ± 2.2 U in HeLa cells, 7.2 ± 1.4 U in a mixed HL60 cell-HUVEC population (ratio 2:1) and 8.5 ± 2.0 in a mixed HeLa cell-HUVEC population (ratio 2:1). Incubation at 37°C for up to 4 hours of tumor cells or HUVEC alone did not produce any change in procoagulant activity. In contrast, co-incubation of tumor cells with HUVEC for 4 hours was followed by a significant increase in procoagulant activity of the mixed cell populations. Addition of supernatants from tumor cells, HUVEC or tumor celI-HUVEC co-cultures to HUVEC or tumor cells showed that the tissue factor-like procoagulant activity generated during coincubation was localized on HUVEC. Interpretation and Conclusions. Our results show that the close interaction of tumor cells with endothelial cells may induce surface expression of tissue factor in the latter. This effect could represent an additional mechanism of clotting activation in patients with cancer.

Original languageEnglish
Pages (from-to)624-628
Number of pages5
JournalHaematologica
Volume87
Issue number6
Publication statusPublished - 2002

Fingerprint

Human Umbilical Vein Endothelial Cells
Thromboplastin
Hemostasis
Endothelial Cells
Neoplasms
HL-60 Cells
Coculture Techniques
HeLa Cells
Population
Cell Culture Techniques
Rabbits
Brain
Tumor Cell Line
Cell Communication
Uterine Cervical Neoplasms
Calibration
Leukemia

Keywords

  • Endothelial cells
  • Tissue factor
  • Tumor cells

ASJC Scopus subject areas

  • Hematology

Cite this

Hemostasis and cancer : Tumor cells induce the expression of tissue factor-like procoagulant activity on endothelial cells. / Maiolo, Anna; Tua, Aldo; Grignani, Guido.

In: Haematologica, Vol. 87, No. 6, 2002, p. 624-628.

Research output: Contribution to journalArticle

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abstract = "Background and Objectives. Clotting activation and thromboembolic manifestations are common features in patients with cancer. The two-way interaction between tumor cells and host cells is of crucial importance in this context. In the present study we investigated the effect of tumor cell-endothelial cell co-culture on the expression of procoagulant activity in the mixed cell populations. Design and Methods. Human tumor cell lines (HL60 promyelocytic leukemia and HeLa uterine cervical cancer) and human umbilical vein endothelial cells (HUVEC) were cultured in vitro according to standard procedures. Procoagulant activity was studied in a coagulometer and was found to be tissue factor-like. A calibration curve was obtained with decreasing concentrations of rabbit brain thromboplastin (RBT) and the procoagulant activity of both tumor cells and HUVEC was expressed as RBT U/105 cells. Results. Before incubation procoagulant activity (mean ± SE) was found to be 0.18 ± 0.04 U in HUVEC, 9.8 ± 1.9 U in HL60 cells, 11.9 ± 2.2 U in HeLa cells, 7.2 ± 1.4 U in a mixed HL60 cell-HUVEC population (ratio 2:1) and 8.5 ± 2.0 in a mixed HeLa cell-HUVEC population (ratio 2:1). Incubation at 37°C for up to 4 hours of tumor cells or HUVEC alone did not produce any change in procoagulant activity. In contrast, co-incubation of tumor cells with HUVEC for 4 hours was followed by a significant increase in procoagulant activity of the mixed cell populations. Addition of supernatants from tumor cells, HUVEC or tumor celI-HUVEC co-cultures to HUVEC or tumor cells showed that the tissue factor-like procoagulant activity generated during coincubation was localized on HUVEC. Interpretation and Conclusions. Our results show that the close interaction of tumor cells with endothelial cells may induce surface expression of tissue factor in the latter. This effect could represent an additional mechanism of clotting activation in patients with cancer.",
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