SPP1 and neoplasm: Note that OPN undergoes proteolytic modification by several proteases like thrombin (21), yielding thrombin-cleaved form of OPN (Thr-OPN), which binds selectively to integrins α4/α9 to exert its functional activity and that these integrins are abundantly expressed in synovial and tumor Mφs (14, 18, 22, 23).