MP87-07 THE BIOLOGICAL RAMIFICATIONS OF PROSTATE CANCER ASSOCIATED CELL FREE DNA: EFFECT ON PLATELET FUNCTION AND DISEASE PROGRESSION

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III1 Apr 2017MP87-07 THE BIOLOGICAL RAMIFICATIONS OF PROSTATE CANCER ASSOCIATED CELL FREE DNA: EFFECT ON PLATELET FUNCTION AND DISEASE PROGRESSION Mackenzie Adams, James Henderson, Mathew Lee, Todd Morgan, Ganesh Palapattu, and Alexander Zaslavsky Mackenzie AdamsMackenzie Adams More articles by this author , James HendersonJames Henderson More articles by this author , Mathew LeeMathew Lee More articles by this author , Todd MorganTodd Morgan More articles by this author , Ganesh PalapattuGanesh Palapattu More articles by this author , and Alexander ZaslavskyAlexander Zaslavsky More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2711AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The risk of developing venous thromboembolic events (VTE) is increased up to 4-fold in in men diagnosed with metastatic prostate cancer (PCa). While the precise reasons for this are unknown previous work has established the capacity of platelets (clot initiators) to absorb factors from the bloodstream that may alter platelet functions. Notably, one such factor, cell free DNA (cfDNA) has been shown to strongly correlate with disease severity and outcome. In this study, we sought to examine the effects of cfDNA from men with aggressive PCa on platelets in the context of clot formation and disease progression. METHODS Platelets were isolated from venous blood of 10 men with metastatic castration resistant prostate cancer (mCRPC). Platelet aggregation in response to agonists (i.e. thrombin and collagen) was established using platelet aggregometer. Platelet ability to bind to cancer cells (in vitro) was determined using flow cytometry. Platelet effect on prostate tumor growth in vivo was assessed using human platelet transfusions into 3 different PCa mouse models (intracardiac, subcutaneous, and orthotopic) in combination with standard bioluminescence techniques. RESULTS We assessed the effects of tumor associated nucleic acids on circulating platelets. We found that PCa derived cfDNA - loaded platelets were more reactive to agonists (thrombin and collagen), vs. unloaded platelets, making them more susceptible to spontaneous clot formation. We established that platelets from men with mCRPC (10 men) were significantly (p<0.001) more adherent to cancer cells in vitro as compared to platelets from healthy controls. Addition of nucleic acids (i.e. DNA) to healthy donor platelets in vitro converted them to be more thrombogenic and similar to platelets from men with mCRPC. Finally, we observed that platelets from men with mCRPC strongly induced cell proliferation and tumor growth in vivo (p<0.005), as compared to platelets from healthy controls. CONCLUSIONS High levels of cancer associated cfDNA have been previously demonstrated to correlate with poor prognosis and increased risk of VTE in men with PCa. Intriguingly, we found that PCa associated cfDNA modulates platelet behavior, revealing, for the first time, a potential molecular basis for Trousseau syndrome in PCa. Further, our findings also shed new light on how cfDNA may alter cancer growth via modulating platelets in the tumor microenvironment. Taken together, our study provides novel insights into the possible biological consequences of cfDNA seen in the advanced cancer state. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1168 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Mackenzie Adams More articles by this author James Henderson More articles by this author Mathew Lee More articles by this author Todd Morgan More articles by this author Ganesh Palapattu More articles by this author Alexander Zaslavsky More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...