Abstract 1051 Factor XII Directly Impacts Thrombin-Antithrombin Complex Levels in Mice with Epithelial Ovarian Cancer
Year: 2024
Type: conference-abstract
Abstract: High grade serous epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer and has one of the highest rates of venous thromboembolic (VTE) complications. An estimated 5–25% of ovarian cancer patients will develop VTE within the first two years of cancer diagnosis and these women will have lower survival rates than cancer patients without VTE. The prothrombotic potential of EOC has been directly linked to overexpression of coagulation Factor XII (FXII) and proinflammatory chemokines that contribute to exuberant thrombin activity in circulation and the tumor microenvironment. Our lab has demonstrated that FXII contributes to the development of deep vein thrombosis (DVT) through distinct zymogen and enzymatic (FXIIa) functions, promoting neutrophil trafficking at sites of inflammation and venous stasis, and amplifying thrombin formation. More recently, we found that EOC tumor-bearing mice lacking FXII (FXII -/-) fail to develop extensive EOC dissemination and ascites accumulation compared to wild type (WT) littermates. Through this experiment, we are asking if targeted inhibition of FXII can bi-directionally reduce ovarian cancer tumor progression and VTE complications. To induce EOC, a single cell suspension of murine ovarian cancer cells was prepared and injected intraperitoneally in C57BL/6J wild type (WT) and FXII -/- female mice. Mice were monitored for tumor development between a week post-injection and 6 weeks. 4 weeks post-tumor induction, thrombi were induced in tumor-bearing WT and FXII -/- mice via stenosis of the inferior vena cava. To determine if tumor induction led to activation of the coagulation system, platelet-poor plasma was collected by centrifugation of whole blood and used for measurement of thrombin-antithrombin (TAT) complex levels through ELISA. Our hypothesis is that we will observe a decrease in TAT complex levels 4 weeks post-injection in FXII -/- mice in comparison to their WT counterparts. Our results show that in 20-fold dilution of plasma, the concentration of TAT complexes is 285.08 pg/mL in WT mice and 142.03 pg/mL in FXII -/- mice 4 weeks post-injection, which suggests that FXII plays an important role in driving cancer-associated VTE. I would like to acknowledge the Case Comprehensive Cancer Center for funding my summer research project through the CanSUR program at Case Western Reserve University.
Source: Journal of Biological Chemistry
Institution: Case Western Reserve University
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,800
OpenAlex ID: W4393167662