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 α3 and 6 in HepG2 cells.

Anti-cancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer

“…Exosomal cargoes have been found to correlate with the physiological state of donor cells. Isolated tonsil-derived MSCsecreted EVs possessed a tumor suppressive effect on the human liver cancer cell line HepG2 [44]. Due to their multipotency, MSC-derived exosomes could also be tumorigenic [45].…”

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

“…MSC-EVs loaded with miR-193a downregulated focal adhesion kinase (FAK) to inhibit colon cancer cell proliferation, migration, and invasion [ 49 ]. For tumor growth, MSC-EVs showed pro-tumor effects in lung and gastric cancers and anti-tumor function on liver cancer [ 50 , 51 , 52 ]. In hepatocellular carcinoma, MSC-EVs carrying miRNA-20a-3p can target cFLIP to promote tumor apoptosis [ 53 ].…”