Extracellular vesicles from tonsil-derived mesenchymal stromal cells show anti-tumor effect via miR-199a-3p

Abstract

Mesenchymal stem cells (MSCs) are mesoderm-originated adult SCs that possess multidirectional differentiation potential. MSCs migrate to injured tissue and secrete a range of paracrine factors that induce regeneration in damaged tissue and exert immune modulation. Because tumor progression is dependent on cross-talk between the tumor and its microenvironment, MSCs also produce extra-cellular vesicles (EVs) that mediate information transfer in the tumor microenvironment. However, the effect of MSC-derived EVs on tumor development and progression is still controversial. To date, tonsil-derived MSCs (T-MSCs) have been shown to possess all the defined characteristics of MSCs and show distinctive features of differential potential and immune modulation. To observe the effect of soluble mediators from T-MSCs on tumor growth, human liver cancer cell line (HepG2) cells were injected into nude mice and HepG2 cell scratch migration assay was performed using conditioned medium (CM) of T-MSCs. T-MSC CM inhibited tumor growth and progression and it was hypothesized that EVs from T-MSCs could inhibit tumor progression. microRNA (miRNA or miR) sequencing using five different origins of T-MSC-derived EVs was performed and highly expressed miRNAs, such as miR-199a-3p, miR-214-3p, miR-199a-5p and miR-199b-5p, were selected. T-MSCs inhibited tumor growth and HepG2 cell migration, potentially via miR-199a-3p targeting CD151, integrin alpha 3 and 6 in HepG2 cells.