FIGURE 5.

Blocking sEV and inhibition of ISG15 reduces ovarian tumour progression and metastasis. (a–d) Significant reduction in tumour growth and metastasis was observed in DAP5 (100 ppm in animal feed) treatment (ISG15 inhibitor) and in amiloride (AME)+ carboplatin (CP‐ 2 mg/kg b.wt.) treated group in orthotopic nude mice injected with luciferase stable transfected TR127 cells when compared to treatment with sEV inhibitor (AME‐ 2 mg/kg/ twice a week) alone for 5 weeks (n = 4 mice ± SD). (e and f) Tumour progression in immunocompetent mouse models injected orthotopically with immortalized ID8 cells, (1 × 10⁶ cells) treated with amiloride (2 mg/kg/twice a week) or DAP5‐100 ppm in combination with carboplatin (CP‐ 2 mg/kg b.wt., n = 3 mice ± SD). (g) sEV formation in amiloride treated mouse tissue compared to untreated tumour tissue as observed by TEM. (h and i) sEV quantification by image stream flow cytometry on POCC control and TR127‐ISG15‐Kd cells treated with Texas‐red labelled carboplatin (n = 3). The overlay of the Tr‐CP on the FITC+ve vesicle is shown in the inner square on the graph.