Poster Presentation Australasian Extracellular Vesicles Conference 2018

Extracellular vesicles from non-tumourigenic and tumourigenic prostate cells affect thrombin clot formation in vitro (#87)

Joshua Brzozowski 1 2 , Fiona Scorgie 2 3 , Helen Jankowski 1 2 , Siobhan McCague 2 , Benjamin Munro 2 4 , Danielle Bond 1 2 , Christopher Scarlett 2 4 , Kathryn Skelding 1 2 , Lisa Lincz 1 2 3 , Judith Weidenhofer 1 2
  1. School of Biomedical Sciences & Pharmacy and the Priority Research Centre, Innovation and Translation, University of Newcastle, Newcastle, NSW, Australia
  2. HCRA & Hunter Medical Research Institute, Newcastle, NSW, Australia
  3. Hunter Haematology Research Group, Calvary Mater Newcastle, Newcastle, NSW, Australia
  4. School of Environmental & Life Sciences, University of Newcastle, Ourimbah, NSW, Australia

Prostate cancer patients commonly present with coagulopathies, either following treatment or as the presenting condition of disease. Extracellular vesicles (EVs) including microparticles and microvesicles, are known to enhance coagulation, however the effect of smaller EVs in coagulation is unknown. The tetraspanins CD9 and CD151 have known roles in coagulation, particularly through interactions with integrins and platelets and are commonly found on EVs. CD9 and CD151 are also implicated in prostate cancer, with CD9 supressing and CD151 enhancing metastasis. Using the in vitro calibrated automated thrombogram model, the kinetics of thrombin generation in human plasma mixed with EV samples from tumourigenic and non-tumourigenic prostate cells was determined. In addition, the specific effects of CD151 and CD9 were assessed through the addition of EVs secreted from non-tumourigenic cells modified to have increased CD151 or decreased CD9 expression. EVs from tumourigenic prostate cells showed conflicting effects, with those from the PC3 cell line supressing thrombin formation and those from the WPE1-NB26 cell line enhancing some features of thrombus formation. EVs from the non-tumourigenic RWPE1 cell line generally enhanced thrombus formation. Interestingly EVs from RWPE1 cells overexpressing CD151 decreased lagtime, time to peak and increased peak height and endogenous thrombus potential compared to EVs from the vector control cell line. These findings suggest that EVs secreted from prostate cancer cells are involved in the development of coagulopathies in prostate cancer, and that the abundance of tetraspanins on EVs may be the main determinant of what effect EVs have on thrombus formation.