Tumor-secreted exosomal Wnt2B activates fibroblasts to promote cervical cancer progression

The activation of stromal fibroblasts into cancer-associated fibroblasts (CAFs) has been suggested to promote primary tumor growth and progression; however, the mechanisms underlying the crosstalk between tumors and fibroblasts that drives stromal heterogeneity remain unknown. Here, we show that high Wnt2B levels were positively correlated with the number of CAFs in cervical cancer (CC). More importantly, Wnt2B was characteristically enriched in CC cell-secreted exosomes and transferred into fibroblasts to promote fibroblast activation via Wnt/beta-catenin signaling, and inhibiting exosomal release or the Wnt/beta-catenin signaling pathway diminished the activation induced by exosomal Wnt2B. Moreover, circulating exosomal Wnt2B also promoted CAF conversion in vitro and its expression was significantly higher in CC patients. In conclusion, our findings indicate that CC cell-derived Wnt2B can induce the activation of fibroblasts into CAFs, mainly via exosome-dependent secretion, thus providing directions for the development of diagnostic and therapeutic targets for CC progression.

Automated summary

In this study, it was found that Wnt2B secreted by cervical cancer cells promotes the activation of fibroblasts into cancer-associated fibroblasts (CAFs) through exosome-mediated transfer. The circulating exosomal Wnt2B also contributes to CAF conversion in vitro and is significantly elevated in cervical cancer patients. These findings provide insights for the development of diagnostic and therapeutic targets for cervical cancer progression.