Abstract 20227: Impact of Solid Tumors on Venous Thrombosis: A Novel Unified Model to Understand Cancer-Associated Thrombosis
Cancer-associated thrombosis (C-AT) is poorly understood due to the lack of an animal model that combines these two pathologies in one biological system. Studies examining the incidence and predictors of venous thrombosis (VT) in patients with cancer (CA) suggest that VT incidence varied by CA type from 19.2% in pancreatic CA to 8.2% in bladder CA. We have developed a unified animal model of C-AT to allow for investigations across different CA types with a reproducible VT model.
Methods: The effects of different CAs on VT were investigated by injecting one million cells of either pancreatic CA (AsPC-1) or bladder CA (UC9) subcutaneously (SC) in NOD SCID mice. Control animals were injected with a vehicle. Tumor growth was monitored with external caliper and non-contrast T2-weighted MRI until a volume of 500 mm3 was reached (conditioning), at which point VT was induced in all mice using the ligation model. Thrombus volume was monitored post VT induction by MRI, and compared to thrombus weight (TW) at harvest.
Results: All animals survived both diseases. The presence of pancreatic and bladder CA increased TW by 203% and 153%, respectively (AsPC-1: non-CA 31±2 mg, CA 63±6 mg; UM-UC-9: non-CA 30±2 mg, CA 46±3 mg). MRI measurements confirmed the TW results in volume (AsPC-1 45±5 mm3; UC9 39±2 mm3).
Conclusions: CA and VT were successfully combined in one animal survival model without complications, providing the first unified mouse model for studying C-AT. Using this model, we observed that CA triggers an increase in thrombus size, with significantly larger effects from pancreatic CA compared to bladder CA. These data correlate with clinical observations of pancreatic CA patients being more prone to develop VT. The SC location allows for caliper determination of tumor volume for appropriate timing of VT induction. MRI confirmed conditioning at these volumes, and could enable the use of heterotopic models. Future studies are planned to use this novel unified model for determining mechanisms and potential targets for C-AT.
Author Disclosures: G. Lorenzatti Hiles: None. A.L. Cates: None. O.R. Palmer: None. A. Emamdjomeh: None. C.B. Chiu: None. L. El-Sawy: Consultant/Advisory Board; Modest; European Egyptian Pharmaceuticals (EEPI)). M.L. Day: Consultant/Advisory Board; Modest; European Egyptian Pharmaceuticals (EEPI)). J.M. Greve: None. J.A. Diaz: Other; Modest; Board of Directors, American Venous Forum.
- © 2016 by American Heart Association, Inc.