In fact, the interaction between extracellular matrix deposited OPN and cell adhesion molecules, such as αvβ3 integrins which are overexpressed in BALB-neuT tumors [98], increases both the expression of VEGF in ECs, allowing neovascularization, and the activation of connective tissue growth factor and cysteine-rich angiogenic inducer 61(CYR61), which enhances neovascularization and mammary tumor growth in vivo [168]. This evidence concerns the gene SPP1 and breast cancer.