In this study, we observed that the dual role of the CAFs is mediated by IL-33, that is, normal supporting fibroblasts that are called persevered or putative CAFs for the maintenance of hemostasis, once involved in carcinogenesis, will through their crosstalk with cancer cells, trigger the IL-33/CXCR4 signaling circuit and can contribute to tumor aggressiveness. This evidence concerns the gene CXCR4 and neoplasm.