SPP1 and cancer: These cells, termed CSCs, have a crucial role in cancer initiation, with one CSC capable of giving rise to an entire tumour.39 CSCs are predominantly dormant so they are naturally resistant to anti-proliferative chemotherapy and therefore difficult to eradicate, and might be responsible for relapse years after initial treatment.40 CAF-derived chemokine (CC motif) ligand 2 (CCL2), IL-6, hepatocyte growth factor (HGF), osteopontin (OPN) and stromal cell-derived factor 1 (SDF-1) each independently induce the CSC phenotype in epithelial cells.41–43