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

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
    • CME
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CCR Focus Archive
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Breast Cancer
      • Clinical Trials
      • Immunotherapy: Facts and Hopes
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • 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
  • My Cart

Search

  • Advanced search
Clinical Cancer Research
Clinical Cancer Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
    • CME
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CCR Focus Archive
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Breast Cancer
      • Clinical Trials
      • Immunotherapy: Facts and Hopes
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Cancer Therapy: Preclinical

Zoledronic Acid Has Differential Antitumor Activity in the Pre- and Postmenopausal Bone Microenvironment In Vivo

Penelope D. Ottewell, Ning Wang, Hannah K. Brown, Kimberly J. Reeves, C. Anne Fowles, Peter I. Croucher, Colby L. Eaton and Ingunn Holen
Penelope D. Ottewell
1Academic Unit of Clinical Oncology, Department of Oncology, 2Academic Unit of Bone Biology, Department of Human Metabolism, University of Sheffield, Sheffield, United Kingdom; and 3Musculoskeletal Medicine Division, Garvan Institute of Medical Research, Sidney, New South Wales, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ning Wang
1Academic Unit of Clinical Oncology, Department of Oncology, 2Academic Unit of Bone Biology, Department of Human Metabolism, University of Sheffield, Sheffield, United Kingdom; and 3Musculoskeletal Medicine Division, Garvan Institute of Medical Research, Sidney, New South Wales, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hannah K. Brown
1Academic Unit of Clinical Oncology, Department of Oncology, 2Academic Unit of Bone Biology, Department of Human Metabolism, University of Sheffield, Sheffield, United Kingdom; and 3Musculoskeletal Medicine Division, Garvan Institute of Medical Research, Sidney, New South Wales, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kimberly J. Reeves
1Academic Unit of Clinical Oncology, Department of Oncology, 2Academic Unit of Bone Biology, Department of Human Metabolism, University of Sheffield, Sheffield, United Kingdom; and 3Musculoskeletal Medicine Division, Garvan Institute of Medical Research, Sidney, New South Wales, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Anne Fowles
1Academic Unit of Clinical Oncology, Department of Oncology, 2Academic Unit of Bone Biology, Department of Human Metabolism, University of Sheffield, Sheffield, United Kingdom; and 3Musculoskeletal Medicine Division, Garvan Institute of Medical Research, Sidney, New South Wales, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter I. Croucher
1Academic Unit of Clinical Oncology, Department of Oncology, 2Academic Unit of Bone Biology, Department of Human Metabolism, University of Sheffield, Sheffield, United Kingdom; and 3Musculoskeletal Medicine Division, Garvan Institute of Medical Research, Sidney, New South Wales, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Colby L. Eaton
1Academic Unit of Clinical Oncology, Department of Oncology, 2Academic Unit of Bone Biology, Department of Human Metabolism, University of Sheffield, Sheffield, United Kingdom; and 3Musculoskeletal Medicine Division, Garvan Institute of Medical Research, Sidney, New South Wales, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ingunn Holen
1Academic Unit of Clinical Oncology, Department of Oncology, 2Academic Unit of Bone Biology, Department of Human Metabolism, University of Sheffield, Sheffield, United Kingdom; and 3Musculoskeletal Medicine Division, Garvan Institute of Medical Research, Sidney, New South Wales, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1078-0432.CCR-13-1246 Published June 2014
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Purpose: Clinical trials in early breast cancer have suggested that benefits of adjuvant bone-targeted treatments are restricted to women with established menopause. We developed models that mimic pre- and postmenopausal status to investigate effects of altered bone turnover on growth of disseminated breast tumor cells. Here, we report a differential antitumor effect of zoledronic acid (ZOL) in these two settings.

Experimental design: Twleve-week-old female Balb/c-nude mice with disseminated MDA-MB-231 breast tumor cells in bone underwent sham operation or ovariectomy (OVX), mimicking the pre- and postmenopausal bone microenvironment, respectively. To determine the effects of bone-targeted therapy, sham/OVX animals received saline or 100 μg/kg ZOL weekly. Tumor growth was assessed by in vivo imaging and effects on bone by real-time PCR, micro-CT, histomorphometry, and measurements of bone markers. Disseminated tumor cells were detected by two-photon microscopy.

Results: OVX increased bone resorption and induced growth of disseminated tumor cells in bone. Tumors were detected in 83% of animals following OVX (postmenopausal model) compared with 17% following sham operation (premenopausal model). OVX had no effect on tumors outside of bone. OVX-induced tumor growth was completely prevented by ZOL, despite the presence of disseminated tumor cells. ZOL did not affect tumor growth in bone in the sham-operated animals. ZOL increased bone volume in both groups.

Conclusions: This is the first demonstration that tumor growth is driven by osteoclast-mediated mechanisms in models that mimic post- but not premenopausal bone, providing a biologic rationale for the differential antitumor effects of ZOL reported in these settings. Clin Cancer Res; 20(11); 2922–32. ©2014 AACR.

See related article by Wright and Guise, p. 2817

Footnotes

  • Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

  • Received May 9, 2013.
  • Revision received December 18, 2013.
  • Accepted March 4, 2014.
  • ©2014 American Association for Cancer Research.
View Full Text
PreviousNext
Back to top
Clinical Cancer Research: 20 (11)
June 2014
Volume 20, Issue 11
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Clinical 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.
Zoledronic Acid Has Differential Antitumor Activity in the Pre- and Postmenopausal Bone Microenvironment In Vivo
(Your Name) has forwarded a page to you from Clinical Cancer Research
(Your Name) thought you would be interested in this article in Clinical Cancer Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Zoledronic Acid Has Differential Antitumor Activity in the Pre- and Postmenopausal Bone Microenvironment In Vivo
Penelope D. Ottewell, Ning Wang, Hannah K. Brown, Kimberly J. Reeves, C. Anne Fowles, Peter I. Croucher, Colby L. Eaton and Ingunn Holen
Clin Cancer Res June 1 2014 (20) (11) 2922-2932; DOI: 10.1158/1078-0432.CCR-13-1246

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Zoledronic Acid Has Differential Antitumor Activity in the Pre- and Postmenopausal Bone Microenvironment In Vivo
Penelope D. Ottewell, Ning Wang, Hannah K. Brown, Kimberly J. Reeves, C. Anne Fowles, Peter I. Croucher, Colby L. Eaton and Ingunn Holen
Clin Cancer Res June 1 2014 (20) (11) 2922-2932; DOI: 10.1158/1078-0432.CCR-13-1246
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
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Authors' Contributions
    • Grant Support
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • TAZ is a Potent Mediator of aRMS Tumorigenesis
  • Targeting HER2 with Osimertinib in NSCLC
  • Combined VEGF/EGFR Inhibition
Show more Cancer Therapy: Preclinical
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • CCR Focus Archive
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Clinical Cancer Research

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

Copyright © 2021 by the American Association for Cancer Research.

Clinical Cancer Research
eISSN: 1557-3265
ISSN: 1078-0432

Advertisement