MP81-14 EXOSOMES SECRETED BY PLACENTAL STEM CELLS SELECTIVELY INHIBIT GROWTH OF PROSTATE CANCER CELLS

Abstract

You have accessJournal of UrologyStem Cell Research: Stem Cell Research II1 Apr 2018MP81-14 EXOSOMES SECRETED BY PLACENTAL STEM CELLS SELECTIVELY INHIBIT GROWTH OF PROSTATE CANCER CELLS Taylor Peak, Prakash Praharaj, Gati Panigrahi, Yixin Su, Isabel Schlaepfer, Ravi Singh, Donald Vander Griend, Julie Allickson, Anthony Atala, and Gagan Deep Taylor PeakTaylor Peak More articles by this author , Prakash PraharajPrakash Praharaj More articles by this author , Gati PanigrahiGati Panigrahi More articles by this author , Yixin SuYixin Su More articles by this author , Isabel SchlaepferIsabel Schlaepfer More articles by this author , Ravi SinghRavi Singh More articles by this author , Donald Vander GriendDonald Vander Griend More articles by this author , Julie AllicksonJulie Allickson More articles by this author , Anthony AtalaAnthony Atala More articles by this author , and Gagan DeepGagan Deep More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2722AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES For patients who develop castrate-resistant prostate cancer (CRPC), enzalutamide represents an androgen deprivation therapy (ADT) utilized by clinicians. However, as with other forms of ADT, patients become resistant to enzalutamide, prompting the need to identify agents with a novel mechanism of action. We identified exosomes derived from c-kit selected placental stem cells (PLSC) as a therapeutic option for CRPC. METHODS We isolated exosomes from conditioned media of PLSC by ultracentrifugation and characterized size distribution and number by nanoparticle tracking analysis, as well as protein and lipid content by Mass Spectrometry. We treated enzalutamide-sensitive(S) and resistant(R) C4-2B, CWR-R1, LNCaP cells, as well as non-neoplastic prostate (PREC-1 and PWR-R1) and fibroblast (M3T3) cells with PLSC exosomes. We tested the cytotoxicity of exosomes on all cell lines by MTT Assay. We then performed a clonogenic assay using the same dose of PLSC exosomes on C4-2B-S, C4-2B-R, and PWR-R1. Finally, to understand the mechanism behind their biological efficacy, we treated C4-2B cells with exosomes and examined changes in protein expression. RESULTS PLSC exosomes were loaded with high concentrations of saturated long chain fatty acids (LCFAs) (A). These exosomes inhibited cell viability of all prostate cancer cells lines by 30-50%. In addition, there was no effect on the viability of non-neoplastic cells. PLSC exosomes significantly inhibited clone formation in C4-2B-sensitive and resistant cells by 47% and 64%, respectively (B). There was no inhibition of clone formation in the non-neoplastic PWR-R1 cell line (C). Based on our protein and lipid data of PLSC exosomes, we explored the retinoic acid receptor pathway as a potential mechanism of action. We found that after treating C4-2B cells with exosomes, there was a significant increase in expression of retinoic acid receptor γ. CONCLUSIONS PLSC exosomes selectively inhibit growth of enzalutamide-sensitive and resistant cell lines, without affecting the growth of non-cancerous cells. This growth inhibition is associated with an increase in retinoid acid receptor γ, a known tumor suppressor that is regulated by LCFAs. We propose that the LCFAs loaded in exosomes activate retinoid acid receptor γ, thus suppressing the growth of prostate cancer tumor cells. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1102 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Taylor Peak More articles by this author Prakash Praharaj More articles by this author Gati Panigrahi More articles by this author Yixin Su More articles by this author Isabel Schlaepfer More articles by this author Ravi Singh More articles by this author Donald Vander Griend More articles by this author Julie Allickson More articles by this author Anthony Atala More articles by this author Gagan Deep More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...