Binding of OPN to the above receptors on tumor cells triggers downstream signaling pathways including Ras, Akt, MAPK, Src, FAK and NF-KB [1] that collectively lead to the following in tumor cells: i) invasion to ECM (extracellular matrix) mainly via upregulation of MMPs [19] (matrix metalloproteinases) and uPAs [20] (urokinase plasminogen activator) by OPN; ii) increased migration and adhesion of tumor cells [21]; iii) inhibition of cell death likely through upregulation of anti-apoptosis mediators such as GAS6 [22]; and iv) development of pre-metastatic niche [23]. Here, SPP1 is linked to neoplasm.