Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Experimental and Molecular Therapeutics

Abstract 3187: Role of exosome secretion in the survival of enzalutamide-resistant prostate cancer cells: Syntaxin 6 as a novel therapeutic target

Taylor C. Peak, Nicole P. Kasica, Gati K. Panigrahi, Sierra L. Patterson, Ravi Singh, Ashok K. Hemal, Rhonda L. Bitting and Gagan Deep
Taylor C. Peak
Wake Forest Baptist Medical Center, Winston-Salem, NC.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicole P. Kasica
Wake Forest Baptist Medical Center, Winston-Salem, NC.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gati K. Panigrahi
Wake Forest Baptist Medical Center, Winston-Salem, NC.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sierra L. Patterson
Wake Forest Baptist Medical Center, Winston-Salem, NC.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ravi Singh
Wake Forest Baptist Medical Center, Winston-Salem, NC.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ashok K. Hemal
Wake Forest Baptist Medical Center, Winston-Salem, NC.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rhonda L. Bitting
Wake Forest Baptist Medical Center, Winston-Salem, NC.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gagan Deep
Wake Forest Baptist Medical Center, Winston-Salem, NC.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7445.AM2017-3187 Published July 2017
  • Article
  • Info & Metrics
Loading
Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC

Abstract

Prostate cancer (PCa) is the most commonly diagnosed malignancy in the United States and remains the second leading cause of cancer deaths among American men. PCa deaths are typically the result of metastatic castration-resistant PCa (mCRPC). Recently, enzalutamide (Enz), an oral AR inhibitor, was approved for treating patients with mCRPC, and has significantly improved patient survival. But, invariably all PCa patients eventually develop resistance against Enz and die from mCRPC. Therefore, novel strategies aimed at overcoming Enz-resistance are urgently needed to improve the survival of PCa patients. Exosomes (extracellular vesicle, 40-150 nm in size) have previously been shown to communicate oncogenic signals and to promote growth and metastasis; however, their role in drug resistance has not been fully elucidated. Therefore, we set out to better understand exosomes role in the mechanism underlying Enz-resistance in PCa cells. We isolated exosomes secreted by Enz-sensitive (S) and -resistant (R) PCa cells by ultracentrifugation. Complete characterization of these exosomes followed using nanoparticle tracking analysis (NTA), transmission electron microscopy, proteomics, and western blotting. MTT and trypan blue exclusion assays were used to evaluate cell viability. Results showed that Enz-resistant C4-2B-R cells secreted significantly higher amount (2.67 fold) of exosomes compared to sensitive C4-2B-S cells, but without any significant change in exosome size. Proteomics analysis revealed significantly lesser number and amounts of proteins loaded in exosomes secreted by C4-2B-R cells compared to C4-2B-S cells. Western blotting validated these results, and in general less loading was observed for several exosomal biomarker proteins (e.g. CD63, Lox, TSG101, and MMP9). Of note, AR-V7, a variant of the androgen receptor, was upregulated in C4-2B-R cells as well in their exosomes. In order to better understand the biological significance of increased exosome production with concomitant decreased protein expression, we administered C4-2B-R-derived exosomes to C4-2B-S cells. Interestingly, exosomes from resistant cells significantly reduced the survival of C4-2B-S cells . This suggested not only that the resistant cells were utilizing exosomes to secrete Enz, but that these exosomes were being taken up by the sensitive PCa cells, thus leading to enhanced sensitive cell death. The inhibition of exosome biogenesis in C4-2B-R cells using GW4869 (20 µM) and dimethyl amiloride (1 µg/mL) strongly decreased their cell viability, and also increased their sensitivity towards Enz treatment. We also observed strong upregulation of syntaxin 6 in Enz-resistant C4-2B-R cells. Together, these results identified a unique mechanism underlying drug-resistance, and also offer a novel target to treat Enz-resistant CRPC.

Citation Format: Taylor C. Peak, Nicole P. Kasica, Gati K. Panigrahi, Sierra L. Patterson, Ravi Singh, Ashok K. Hemal, Rhonda L. Bitting, Gagan Deep. Role of exosome secretion in the survival of enzalutamide-resistant prostate cancer cells: Syntaxin 6 as a novel therapeutic target [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3187. doi:10.1158/1538-7445.AM2017-3187

  • ©2017 American Association for Cancer Research.
Previous
Back to top
Cancer Research: 77 (13 Supplement)
July 2017
Volume 77, Issue 13 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Abstract 3187: Role of exosome secretion in the survival of enzalutamide-resistant prostate cancer cells: Syntaxin 6 as a novel therapeutic target
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Abstract 3187: Role of exosome secretion in the survival of enzalutamide-resistant prostate cancer cells: Syntaxin 6 as a novel therapeutic target
Taylor C. Peak, Nicole P. Kasica, Gati K. Panigrahi, Sierra L. Patterson, Ravi Singh, Ashok K. Hemal, Rhonda L. Bitting and Gagan Deep
Cancer Res July 1 2017 (77) (13 Supplement) 3187; DOI: 10.1158/1538-7445.AM2017-3187

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract 3187: Role of exosome secretion in the survival of enzalutamide-resistant prostate cancer cells: Syntaxin 6 as a novel therapeutic target
Taylor C. Peak, Nicole P. Kasica, Gati K. Panigrahi, Sierra L. Patterson, Ravi Singh, Ashok K. Hemal, Rhonda L. Bitting and Gagan Deep
Cancer Res July 1 2017 (77) (13 Supplement) 3187; DOI: 10.1158/1538-7445.AM2017-3187
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Experimental and Molecular Therapeutics

  • Abstract SY14-03: Anaplastic lymphoma kinase (ALK): Normal biology and role in hematopoietic malignancies
  • Abstract SY18-01: Targeting the p53-MDM2 interaction for cancer therapy
  • Abstract SSY01-04: Discovery and validation of genome-wide genetic signatures of chemotherapy susceptibility: A translational model
Show more 3

Poster Presentations - Proffered Abstracts

  • Abstract LB-236: Risk of tMDS/AML after chemotherapy for first primary lymphoid malignancy, 2000-2013
  • Abstract LB-001: Impact of direct physician engagement with racial/ethnic minorities for oncology clinical trial access and accrual model
  • Abstract LB-107: EV-TRACK: transparent reporting and centralizing knowledge of extracellular vesicles to support the validation of extracellular vesicle biomarkers in cancer research
Show more 3

Poster Presentations - Novel Mechanisms 1

  • Abstract 3184: Autophagy regulation by vacuolar-ATPases: A contributing mechanism of chemo-resistance in ovarian cancer
  • Abstract 3171: Analysis of "drug addiction" mechanisms in the drug-resistant ROS1-rearranged cancer cells
  • Abstract 3179: The effect of eribulin resistant mechanism in breast cancer on microenvironment
Show more 3
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement