The effects of coagulation factors and their inhibitors on proliferation and migration in colorectal cancer

Abstract

Background/AimClotting factors promote cancer development. We investigated if coagulation proteins promote proliferation and migration in colorectal cancer (CRC) cell lines and whether their direct inhibitors can attenuate these effects.Materials and MethodsDLD‐1 and SW620 cells were treated with tissue factor (0, 50, 100 and 500 pg/mL ± 10 μg/mL 10H10 [anti‐tissue factor antibody]), thrombin (0.0, 0.1, 1.0 and 10.0 U/mL ± 0.5 μM dabigatran [thrombin inhibitor]) and Factor Xa, FXa (0.0, 0.1, 1.0 and 10.0 U/mL ± 100 ng/mL rivaroxaban [FXa inhibitor]) and their effects on proliferation and migration were quantified using the PrestoBlue® and transwell migration assays, respectively.ResultsThrombin increased proliferation from 48 h treatment compared to its control (48 h 6.57 ± 1.36 u vs. 2.42 ± 0.13 u, p = 0.001, 72 h 9.50 ± 1.54 u vs. 4.50 ± 0.47 u, p = 0.004 and 96 h 10.77 ± 1.72 u vs. 5.57 ± 0.25 u, p = 0.008). This increase in proliferation was attenuated by dabigatran at 72 h (2.23 ± 0.16 u vs. 3.26 ± 0.43 u, p = 0.04).Tissue factor (0 pg/mL 20.7 ± 1.6 cells/view vs. 50 pg/mL 32.4 ± 1.9 cells/view, p = 0.0002), FXa (0.0 U/mL 8.9 ± 1.1 cells/view vs. 10.0 U/mL 17.7 ± 1.7 cells/view, p < 0.0001) and thrombin (0.0 U/mL 8.9 ± 1.3 cells/view vs. 10.0 U/mL 20.2 ± 2.0 cells/view, p < 0.0001) all increased migration compared to their controls. However, their direct inhibitors did not attenuate these increases.ConclusionThrombin, FXa and TF all increase migration in CRC in vitro. Thrombin induced increase in proliferation is abrogated by dabigatran. Dabigatran may have potential as an anti‐cancer therapy in CRC.

Human Muse cells isolated from preterm- and term-umbilical cord delivered therapeutic effects in rat bleomycin-induced lung injury model without immunosuppressant

“…Furthermore, gene expression related to lung- and blood vessel development, cell migration, and cell adhesion was compared. Both preterm- and term-UC-Muse cells exhibited higher expression of genes associated with lung development (e.g., forkhead box F1, forkhead box P4) [ 59 ], cell migration (e.g., coagulation factor III, S1P receptor 1) [ 26 , 60 ], and cell adhesion (e.g., intercellular adhesion molecules 1 and 5) [ 61 ], compared with BM-Muse cells (Fig. 7 C).…”