Cancer-associated fibroblasts promote cell proliferation and invasion via paracrine Wnt/IL1β signaling pathway in human bladder cancer

Bladder cancer (BC) is the most common urinary system malignancy worldwide. However, molecular mechanisms underlying its progression remain largely unexplored. Accumulating evidence indicates that cancer-associated fibroblasts (CAFs), major constituents of tumor stroma, play a key role in development. Herein, we have successfully isolated CAFs and paired normal (NFs) from bladder tissues. We observed conditional medium (CM-CAF) could significantly enhance cell proliferation (p<0.01) invasion capacity lines T24 J82, compared to NFs or 5637 cells (bladder epithelial control). subsequently identified cytokine IL1β enriched CM-CAF, further functional study showed CAF-derived contributes aggressiveness cells. In mechanisms, demonstrated high level capable activating Wnt signaling cells, upregulates expression IL1β, therefore forming paracrine Wnt/IL1β feedback aggressive phenotype addition, treated with CM-CAF alone, together inhibitor XAV939. found inhibition sufficiently abolish oncogenic effect on cancer. conclusion, our data revealed novel mechanism promote human BC through feedback. Inhibition pathway may provide promising target block interaction between CAF