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

Mesenchymal stem cells (MScs) are meso‑ derm‑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 inhib‑ ited 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, poten‑ tially via miR‑199a‑3p targeting cd151, integrin α3 and 6 in HepG2 cells.