The Extracellular Matrix and Vesicles Modulate the Breast Tumor Microenvironment

Abstract

Emerging evidence has shown multiple roles of the tumor microenvironment (TME) components, specifically the extracellular matrix (ECM), in breast cancer development, progression, and metastasis. Aside from the biophysical properties and biochemical composition of the breast ECM, the signaling molecules are extremely important in maintaining homeostasis, and in the breast TME, they serve as the key components that facilitate tumor progression and immune evasion. Extracellular vesicles (EVs), the mediators that convey messages between the cells and their microenvironment through signaling molecules, have just started to capture attention in breast cancer research. In this comprehensive review, we first provide an overview of the impact of ECM in breast cancer progression as well as the alterations occurring in the TME during this process. The critical importance of EVs and their biomolecular contents in breast cancer progression and metastasis are also discussed. Finally, we discuss the potential biomedical or clinical applications of these extracellular components, as well as how they impact treatment outcomes.

Keywords: breast cancer; extracellular matrix; extracellular vesicles.

Figure 1

Breast tissue undergoing tumorigenesis. The basement membrane is a thin layer of pericellular matrix separating the epithelium and the stroma. Following tumorigenesis, a microenvironment is created, supporting tumor progression. Tumor cells surpass the basement membrane, which becomes more permissive in the tumor microenvironment (TME), invade the stroma, and eventually metastasize to distant sites through vasculature.

Figure 2

Structure of extracellular vesicles (EVs). EVs are lipid-bilayer enclosed vesicles secreted by cells to regulate multiple cellular processes. EVs contain and transport a variety of biomolecules, including RNAs, DNAs, miRNAs, soluble proteins, and a system of cytokines.