Resumen de Role of tissue factor expression in thrombin generation by canine tumor cells

Erika J. Gruber, James L. Catalfamo, Tracy Stokol

• OBJECTIVE To measure thrombin generation by high and low tissue factor (TF)–expressing canine cancer cell lines.

  SAMPLE Canine cell lines CMT25 (high TF–expressing mammary gland tumor cell line) and HMPOS (low TF–expressing osteosarcoma cell line).

  PROCEDURES Thrombin generation by cancer cells was measured in pooled normal canine plasma by use of calibrated automated thrombography without added trigger reagents. Results were expressed as lag time, time to peak thrombin concentration, peak thrombin concentration, and total thrombin concentration or thrombin generation potential. Corn trypsin inhibitor, hirudin, and annexin V were used to inhibit contact activation, thrombin formation, and phosphatidylserine activity, respectively. Pooled normal human plasma deficient in coagulation factors VII, VIII, IX, X, XI, or XII was used to assess the role of individual coagulation factors on thrombin generation.

  RESULTS CMT25 generated significantly more thrombin than did HMPOS (mean ± SD, 3,555 ± 604nM thrombin•min and 636 ± 440nM thrombin•min, respectively). Thrombin generation of CMT25 was dependent on factor VII and phosphatidylserine and was independent of contact activation. In contrast, thrombin generation of HMPOS was attributed to contact activation.

  CONCLUSIONS AND CLINICAL RELEVANCE High TF-expressing canine mammary cancer cells generated thrombin in a plasma milieu in vitro in a factor VII- and phosphatidylserine-dependent manner.