SPP1 and neoplasm: Another study also showed that the CAFs freshly isolated from human CRC tumors produced significantly higher levels of CXCL-12, OPN, TGF-β, and hepatocyte growth factor (HGF), which coordinately activated Wnt–β-catenin signaling to induce the expression of the novel CSC marker CD44 variant 6, resulting in an EMT in cancer cells and tumor invasion and metastasis (56).