SPP1 and neoplasm: Interestingly, intensive interactions were found between macrophages and malignant cells, with four of the most commonly reported ligand–receptor pairs CD74-MIF, SPP1-CD44, CD74-COPA and CD74-APP, whose dysregulations are associated with tumor initiation and metastasis (Stein et al., 2007; Orian-Rousseau, 2015).