Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Most tumor tissue is composed of parenchymal tumor cells and tumor stroma. Mesenchymal stem cells (MSCs) can function as precursors for tumor stromal cells, including myofibroblasts, which provide a favorable environment for tumor progression. A close relationship between tumor cells and MSCs in a tumor microenvironment has been described. Exosomes are small membrane vesicles that are enriched with a discrete set of cellular proteins, and are therefore expected to exert diverse biological functions according to cell origin. In the current study, we determined the biological effect of exosomes from two ovarian cancer cell lines (SK-OV-3 and OVCAR-3) on adipose tissue-derived MSCs (ADSCs). Exosome treatment induced ADSCs to exhibit the typical characteristics of tumor-associated myofibroblasts, with increased expression of α-SMA, and also increased expression of tumor-promoting factors (SDF-1 and TGF-β). This phenomenon was correlated with an increased expression of TGF-β receptors I and II. Analysis of TGF-β receptor-mediated downstream signaling pathways revealed that each exosome activated different signaling pathways, showing that exosomes from SK-OV-3 cells increased the phosphorylated form of SMAD2, which is essential in the SMAD-dependent pathway, whereas exosomes from OVCAR-3 cells increased the phosphorylated form of AKT, a representative SMAD-independent pathway. Taken

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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