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Influence of Fibroblasts on Mammary Gland Development, Breast Cancer Microenvironment Remodeling, and Cancer Cell Dissemination

1
Department of Public Health, University of Naples Federico II, 80131 Naples, Italy
2
Department of Experimental and Clinical Medicine, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
3
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
4
Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, 80131 Naples, Italy
5
Department of General, Oncological, Bariatric and Endocrine-Metabolic Surgery, University of Naples Federico II, 80131 Naples, Italy
6
Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(6), 1697; https://doi.org/10.3390/cancers12061697
Received: 20 May 2020 / Revised: 20 June 2020 / Accepted: 23 June 2020 / Published: 26 June 2020
(This article belongs to the Special Issue A Special Issue on Tumor Stroma )
The stromal microenvironment regulates mammary gland development and tumorigenesis. In normal mammary glands, the stromal microenvironment encompasses the ducts and contains fibroblasts, the main regulators of branching morphogenesis. Understanding the way fibroblast signaling pathways regulate mammary gland development may offer insights into the mechanisms of breast cancer (BC) biology. In fact, the unregulated mammary fibroblast signaling pathways, associated with alterations in extracellular matrix (ECM) remodeling and branching morphogenesis, drive breast cancer microenvironment (BCM) remodeling and cancer growth. The BCM comprises a very heterogeneous tissue containing non-cancer stromal cells, namely, breast cancer-associated fibroblasts (BCAFs), which represent most of the tumor mass. Moreover, the different components of the BCM highly interact with cancer cells, thereby generating a tightly intertwined network. In particular, BC cells activate recruited normal fibroblasts in BCAFs, which, in turn, promote BCM remodeling and metastasis. Thus, comparing the roles of normal fibroblasts and BCAFs in the physiological and metastatic processes, could provide a deeper understanding of the signaling pathways regulating BC dissemination. Here, we review the latest literature describing the structure of the mammary gland and the BCM and summarize the influence of epithelial-mesenchymal transition (EpMT) and autophagy in BC dissemination. Finally, we discuss the roles of fibroblasts and BCAFs in mammary gland development and BCM remodeling, respectively. View Full-Text
Keywords: fibroblasts; breast cancer associated fibroblasts (BCAFs); mammary gland; breast cancer microenvironment; ECM remodeling; metastasis fibroblasts; breast cancer associated fibroblasts (BCAFs); mammary gland; breast cancer microenvironment; ECM remodeling; metastasis
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Avagliano, A.; Fiume, G.; Ruocco, M.R.; Martucci, N.; Vecchio, E.; Insabato, L.; Russo, D.; Accurso, A.; Masone, S.; Montagnani, S.; Arcucci, A. Influence of Fibroblasts on Mammary Gland Development, Breast Cancer Microenvironment Remodeling, and Cancer Cell Dissemination. Cancers 2020, 12, 1697.

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