Osteopontin (OPN) is a phosphorylated glycoprotein from the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs). OPN is ubiquitously distributed in many cells and body fluids, and in particular, it is abundantly present in human milk. The biological functions of OPN are featured by the integrin-binding motifs, such as arginine-glycine-aspartic acid and SVVYGLR/SVAYGLK in the protein sequence. Since OPN binds to integrins and is profoundly involved in integrin signaling, it plays important roles in bone development and remodeling, cell adhesion and chemotaxis, and immunologic interactions. Therefore, it is often investigated in relation to immune-related diseases including cancer. OPN derived from cow's milk is considered as a safe food ingredient and is nutritionally comparable to that found in human milk. Hence, it can be a part of breast milk substitutes. However, from the structural or functional viewpoints, OPN in transformed cells representing a pathological feature of cancer shows distinctive molecular behaviors than OPN in milk derived from healthy individuals. This review summarized the structural features, distribution, and nutritional and physiological functions of milk OPN.
