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.
Highlights
Breast carcinoma is the most frequent cancer and cause of cancer-related death in women worldwide, with approximately 2 million new estimated cases and 627.000 deaths in 2018 [1]
We will review the role of ligand-activated peroxisome proliferator-activated receptor γ (PPARγ) on the epithelial/stromal cells and extracellular matrix (ECM) components/extracellular vesicles of the breast cancer microenvironment, highlighting its potential as a novel therapeutic strategy targeting directly cancer cells and/or indirectly disrupting cellular interaction within tumor microenvironment (TME) which sustains breast cancer progression
In this context, contrasting data are reported on the role of PPARγ as tumor suppressor, since it has been reported that antagonizing PPARγ signaling decreases cancer stem cell population in Erb-B2 receptor tyrosine kinase 2/human epidermal growth factor receptor 2 (ERBB2/HER2)-positive human breast cancer and inhibits tumor formation in an animal model [34], whereas PPARγ downregulation has been associated with Wnt/β-catenin upregulation that is a crucial regulator of stem cells, stem progenitors and cell self-renewal [35,36]
Summary
Breast carcinoma is the most frequent cancer and cause of cancer-related death in women worldwide, with approximately 2 million new estimated cases and 627.000 deaths in 2018 [1]. It has been demonstrated that a dynamic interaction existing between breast cancer cells and the other components of the TME impacts breast tumor progression influencing the effectiveness of the therapeutic treatment [4,5]. Targeting both the epithelial cells and the components of the TME has emerged as a new challenge to provide a better outcome for breast cancer patients [4]. We will review the role of ligand-activated PPARγ on the epithelial/stromal cells (cellular part) and extracellular matrix (ECM) components/extracellular vesicles (non-cellular part) of the breast cancer microenvironment, highlighting its potential as a novel therapeutic strategy targeting directly cancer cells and/or indirectly disrupting cellular interaction within TME which sustains breast cancer progression
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