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/β-catenin signaling, and inhibiting exosomal release or the Wnt/β-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.

已建议将基质成纤维细胞活化为癌症相关的成纤维细胞（CAF）可促进原发性肿瘤的生长和进展。然而，驱动基质异质性的肿瘤与成纤维细胞之间的串扰的潜在机制仍然未知。在这里，我们显示高Wnt2B水平与宫颈癌（CC）中CAF的数量呈正相关。更重要的是，Wnt2B在特征上富含CC细胞分泌的外泌体，并转移到成纤维细胞中，以通过Wnt /β-catenin信号传导促进成纤维细胞活化，并且抑制外泌体释放或Wnt /β-catenin信号传导途径减少了由外泌体Wnt2B诱导的活化。此外，循环外泌体Wnt2B在体外也促进CAF转化，在CC患者中其表达明显更高。综上所述，