Natural and Synthetic PPARγ Ligands in Tumor Microenvironment: A New Potential Strategy against Breast Cancer

Int J Mol Sci. 2020 Dec 19;21(24):9721. doi: 10.3390/ijms21249721.

Abstract

Multiple lines of evidence indicate that activation of the peroxisome proliferator-activated receptor γ (PPARγ) by natural or synthetic ligands exerts tumor suppressive effects in different types of cancer, including breast carcinoma. Over the past decades a new picture of breast cancer as a complex disease consisting of neoplastic epithelial cells and surrounding stroma named the tumor microenvironment (TME) has emerged. Indeed, TME is now recognized as a pivotal element for breast cancer development and progression. Novel strategies targeting both epithelial and stromal components are under development or undergoing clinical trials. In this context, the aim of the present review is to summarize PPARγ activity in breast TME focusing on the role of this receptor on both epithelial/stromal cells and extracellular matrix components of the breast cancer microenvironment. The information provided from the in vitro and in vivo research indicates PPARγ ligands as potential agents with regards to the battle against breast cancer.

Keywords: PPARγ ligands; breast cancer; cancer-associated adipocytes; cancer-associated fibroblasts; extracellular matrix components; extracellular vesicles; peroxisome proliferator-activated receptor gamma; tumor endothelial cells; tumor microenvironment; tumor-associated macrophages.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / immunology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Ligands
  • PPAR gamma / metabolism*
  • Signal Transduction
  • Tumor Microenvironment / immunology*

Substances

  • Ligands
  • PPAR gamma