Abstract Number: PB1853
Meeting: ISTH 2020 Congress
Background: Venous thromboembolism is one of the most common complications in patients with digestive tumors and is associated with an increased morbidity and mortality. The bidirectional interaction between the hemostatic system and tumorigenic processes is based on pleiotropic molecules, whose complex effects are not completely known. Hepsin, a serine protease involved in cancer progression and factor VII activation, is one interesting pleotropic molecule that could be considered as a new promising therapeutic target.
Aims: To study the influence of hepsin levels in tumorigenic processes and in plasma hypercoagulability.
Methods: Hepsin overexpression (HPN) was generated in two cancer cell lines: Kato III (gastric carcinoma) and Caco-2 (colorectal adenocarcinoma). Gene silencing was carried out with the ON-TARGETplus system. Hepsin expression levels were evaluated by western blot and qRT-PCR. Migration assays were performed by wound-healing. Invadopodia invasion was analyzed by fluorescence microscopy and the proliferation rate by XTT assay. The FXa generation was analyzed by incubating plasma with the different cell lines. Continuous variables were compared using non-parametric tests.
Results: Kato III-HPN and Caco-2 HPN showed greater migration (p=0.008 and p=0.120, respectively) and invasiveness capacity (p=0.036 and p=0.012, respectively) than the basal cell lines (Fig.1). Cell proliferation only showed a tendency to increase in HPN cells, while hepsin silencing decreased by 36% the procoagulant capacity of Caco-2 and KATOIII, HPN did not influence this procoagulant effect compared to control cell lines (Fig. 2).
Conclusions: Hepsin is involved in the capacity of migration and invasion of gastric and colorectal cancer cell lines. The silencing of the gene associates with a reduction in their procoagulant capacity, and, in FXa generation, prolonged time parameters and decreased peak height. The plasma FVIIa-AT concentration, likely reflecting FVIIa activation, might be coherently modulated. These data suggest that hepsin could be considered as a biomarker of tumor aggressiveness and thrombotic risk in these tumors.
To cite this abstract in AMA style:Rodenas MC, Baroni M, Peñas-Martínez J, Martinelli N, Ortega C, Castagna A, Espín S, Luengo-Gil G, Zaragoza-Huesca D, Corral J, Vicente V, Carmona-Bayonas A, Bernardi F, Martínez-Martínez I. Hepsin Is Involved in the Tumorigenicity and in the Hipercoagulability of Colon and Gastric Cancer Cells [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/hepsin-is-involved-in-the-tumorigenicity-and-in-the-hipercoagulability-of-colon-and-gastric-cancer-cells/. Accessed January 27, 2022.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/hepsin-is-involved-in-the-tumorigenicity-and-in-the-hipercoagulability-of-colon-and-gastric-cancer-cells/