CAFs secrete multiple factors such as TGF-β1, CXCL-12, FGF, POSTN, osteopontin (OPN), hepatocyte growth factor (HGF), IL-6 and IL-22 that directly stimulate the proliferation of tumor cells in vitro and tumor growth in vivo via activation of their respective signaling pathways, i.e., integrin/FAK-src (POSTN), Wnt/β-catenin (HGF and OPN), PI3K/mTOR (CXCL-12, HGF and IL-22), MAPK (IL-6, TGF-β and FGF) or Hippo (EVs) [83,84,85,86,87,88,89,90]. Here, SPP1 is linked to neoplasm.