Abstract
Mesenchymal stem cells are important cells in tumor microenvironment. We have previously demonstrated that IL-17B/IL-17RB signal promoted progression of gastric cancer. In this study, we further explored the effect of IL-17B on mesenchymal stem cells in tumor microenvironment and its impact on the tumor progression. The results showed that IL-17B induced the expression of stemness-related genes Nanog, Sox2, and Oct4 in mesenchymal stem cells and enhanced its tumor-promoting effect. The supernatant from cultured mesenchymal stem cells after treating with exogenous rIL-17B promoted the proliferation and migration of MGC-803, therefor suggesting that rIL-17B might promote mesenchymal stem cells to produce soluble factors. In addition, rIL-17B also activated the NF-κΒ, STAT3, β-catenin pathway in mesenchymal stem cells. Our data revealed a new mechanism that IL-17B enhanced the progression of gastric cancer by activating mesenchymal stem cells.
Highlights
Gastric cancer is one of the most common gastrointestinal malignancies, and the morbidity and mortality of patients with gastric cancer remain high
Human umbilical cord mesenchymal stem cells (HucMSCs) and gastric cancer-derived mesenchymal stem cells (GC-MSCs) were successfully isolated, cultured and characterized as previously described [16].In order to explore whether IL-17B has an effect on MSCs and further influences tumor progression, the hucMSCs and GC-MSCs were treated with rIL-17B for 48 hours, and washed with PBS for two times and incubated for another 48 hours, this conditioned media was collected
1B and 1C, the colony forming and migratory ability were significantly increased in a dose-dependent manner after MGC-803 was stimulated by supernatants, which were collected from hucMSCs and GC-MSCs treated with rIL-17B (Figure 1A–1D). These results suggested the inflammatory cytokines IL-17B could influence the paracrine activity of MSCs and further changed the biological behavior of gastric cancer cells
Summary
Gastric cancer is one of the most common gastrointestinal malignancies, and the morbidity and mortality of patients with gastric cancer remain high. It is evident that the immunomodulatory activity of MSCs is not innate, rather licensed by inflammatory cytokines, and is highly plastic in response to dynamic changes of inflammatory niche, including the concentration of inflammatory cytokines and the kinds of cytokines [4, 5]. Exposure to cytokines such as IFNγ, TNFα, IL-1β or IL-1α is known to enhance the immunosuppressive properties of MSCs [6]. IL-17 can effectively synergize with IFNγ and TNFα in enhancing MSCs immunosuppression by promoting iNOS expression in vivo [8]
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