The effects of chemotherapeutic agents on the regulation of thrombin on cell surfaces.
Thromboembolic disorders are common in cancer patients. Two major contributing factors are central venous catheters for drug delivery and the use of l-aparaginase, which decreases the plasma antithrombin level, but the causes of the hypercoagulable state in these patients are not fully understood. In this study, the T24/83 cell line was used as a model to investigate the effects of chemotherapeutic agents on cell surface thrombin regulation. Plasma thrombin generation and prothrombin consumption was increased in most of the treated cells, particularly vincristine- and adriamycin-treated cells (P < 0.05), compared with controls. However, no free thrombin generation or prothrombin consumption was observed in factor VII (FVII)-depleted plasma. No significant differences in the levels of thrombin-alpha2-macroglobulin (IIa-alpha2M) and thrombin-anti-thrombin (TAT) were observed between controls and any of the treatments, except for vincristine- and adriamycin-treated cells, which showed a significant difference in TAT production (P < 0.05). Also, there was an upregulation in tissue factor (TF) mRNA expression in etoposide-, methotrexate- and vincristine-treated monolayers compared with controls, as well as an upregulation in TF protein production in vincristine-treated cells. The data suggests that thrombin generation occurs via the extrinsic (TF-dependent) coagulation pathway on cell surfaces and that some chemotherapeutic agents are able to upregulate TF mRNA and protein expression in T24/83 cells.
Paredes
Nethnapha
N
Henderson Research Centre, Hamilton, Ontario, Canada.
Xu
Ling
L
Berry
Leslie R
LR
Chan
Anthony K C
AK
D000970:Antineoplastic Agents / Q000009:adverse effects*; D000991:Antithrombins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D004317:Doxorubicin / Q000009:adverse effects; D005047:Etoposide / Q000009:adverse effects; D006801:Humans; D008727:Methotrexate / Q000009:adverse effects; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000032:analysis / Q000378:metabolism*; D013927:Thrombosis / Q000139:chemically induced*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms; D014750:Vincristine / Q000009:adverse effects; D000511:alpha-Macroglobulins / Q000378:metabolism
D000970:Antineoplastic Agents; D000991:Antithrombins; D000511:alpha-Macroglobulins; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D011516:Prothrombin; D013925:Thromboplastin; D013917:Thrombin; D008727:Methotrexate