Aside from TGF-β, osteopontin (OPN), IL-1β and IL-6, secreted by cancer or immune cells, induce the conversion of stromal fibroblasts to CAFs by activating downstream TGF-β/Smads, NF-kB signaling, and signal transducer and activator of transcription (STAT)3 that are pivotal for modulating expression of genes linked to the CAF lineage [98]. Here, SPP1 is linked to cancer.