title: The effects of chemotherapeutic agents on the regulation of thrombin on cell surfaces.
abstract: 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.
authors.affiliation: Henderson Research Centre, Hamilton, Ontario, Canada.
authors.forename: Nethnapha
authors.initials: N
authors.lastname: Paredes
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Berry
authors.forename: Anthony K C
authors.initials: AK
authors.lastname: Chan
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D000991:Antithrombins; D000511:alpha-Macroglobulins; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D011516:Prothrombin; D013925:Thromboplastin; D013917:Thrombin; D008727:Methotrexate