Systemic PPARγ Antagonism Reduces Metastatic Tumor Progression in Adipocyte-Rich Bone in Excess Weight Male Rodents

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Anastasia Gaculenko - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Gasper Gregoric - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Vanessa Popp - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Lisa Seyler - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Mark Ringer - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Katerina Kachler - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Zhengquan Wu - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Wadim Kisel - , University Center for Orthopedics, Trauma and Plastic Surgery (Author)
  • Christine Hofbauer - , National Center for Tumor Diseases (Partners: UKD, MFD, HZDR, DKFZ), National Center for Tumor Diseases (NCT) Heidelberg, National Center for Tumor Diseases (NCT) Dresden (Author)
  • Lorenz C Hofbauer - , Department of internal Medicine 3, University Hospital Carl Gustav Carus Dresden (Author)
  • Michael Uder - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Georg Schett - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Tobias Bäuerle - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Aline Bozec - , Friedrich-Alexander University Erlangen-Nürnberg (Author)

Abstract

Primary tumors are widely associated with an excess in body fat. The role of adipose tissue on tumor cell homing to bone is yet poorly defined. In this study, we aimed to assess whether bone colonization by tumor cells is favored by an adipocyte-rich bone marrow. We delineated the accompanying alterations of the bone microenvironment and established a treatment approach that interferes with high fat diet (HFD)-induced bone metastasis formation. We were able to show that adipocytes affect skeletal tumor growth in a metastatic model of breast cancer in male rats and melanoma in male mice as well as in human breast cancer bone biopsies. Indeed, HFD-induced bone marrow adiposity was accompanied by accelerated tumor progression and increased osteolytic lesions. In human bone metastases, bone marrow adiposity correlated with tumor cell proliferation. By antagonization of the adipocyte differentiation and storage pathway linked to the peroxisome proliferator-activated receptor gamma (PPARγ) with bisphenol-A-diglycidylether (BADGE), we were able to decelerate tumor progression and subsequent osteolytic damage in the bones of two distinct metastatic animal models exposed to HFD. Overall these data show that adipose tissue is a critical factor in bone metastases and cancer-induced bone loss. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Details

Original languageEnglish
Pages (from-to)2440-2452
Number of pages13
JournalJournal of Bone and Mineral Research
Volume36
Issue number12
Publication statusPublished - Dec 2021
Peer-reviewedYes

External IDs

Scopus 85113582898
ORCID /0000-0002-8691-8423/work/142236020

Keywords

Sustainable Development Goals

Keywords

  • Adipocytes, Animals, Bone Neoplasms/drug therapy, Breast Neoplasms/pathology, Diet, High-Fat, Disease Progression, Male, Mice, Neoplasm Metastasis, Overweight, PPAR gamma/antagonists & inhibitors, Rats, Tumor Microenvironment