Mesenchymal Stem Cell-Derived Extracellular Vesicles: Pleiotropic Impacts on Breast Cancer Occurrence, Development, and Therapy

Abstract

Breast cancer (BC) is one of the most devastating cancers, with high morbidity and mortality, among the female population worldwide. In BC, mesenchymal stem cells (MSCs), as pluripotent stromal stem cells, play a significant role in TME formation and tumor progression. Recently, an increasing number of studies have demonstrated that extracellular vesicles (EVs) are essential for the crosstalk between MSCs and BC cells. MSC-derived EVs (MSC-EVs) can deliver a diversity of molecules, including lipids, proteins, and nucleic acids, etc., to target cells, and produce corresponding effects. Studies have demonstrated that MSC-EVs exert both inhibitory and promotive effects in different situations and different stages of BC. Meanwhile, MSC-EVs provide novel therapeutic options for BC, such as EVs as carriers for drug delivery. Therefore, in this review, we summarize the role of MSC-EVs in BC progression and application in clinical treatment, in the hope of providing a basis for further research.

Keywords: breast cancer; mesenchymal stem cell-derived extracellular vesicles; progression; therapeutic strategies.

Figure 1

Various sources of MSCs and the generation of EVs. MSCs are mainly originated from adipose tissue, dental pulp, bone marrow, umbilical cord, and placenta. Inward budding formed early endosomes matured to form multivesicular bodies, which fuse with plasma membrane release exosomes. Exosomes (30–150 nm) are EVs contains miRNA, protein, lipid, and DNA. Microvesicles (50–1000 nm) are EVs released directly from the plasma membrane.

Figure 3

Naturally occurring and engineered MSC-EVs loaded with endogenous or exogenous cargos for therapeutic purposes. Naturally occurring MSC-EVs contain functional components that inhibit BC development. MSCs can be modified to produce EVs loaded with miRNAs, proteins, or anticancer drugs. Exogenous cargos, such as miRNA and chemotherapeutic drugs, can be loaded into MSC-EVs through engineering techniques. Naturally occurring and engineered MSC-EVs can act on BC to produce therapeutic effects.

Figure 2

The molecular mechanisms of MSC-EVs cargos in breast cancer development. This figure depicts how the EVs interact with the recipient cells and the molecular mechanisms by which cargos loaded in EVs affect breast cancer cells, including proliferation, autophagy, apoptosis, aggressiveness, angiogenesis, immune regulation, dormancy, and drug resistance.